LEPROSY

Anthrax Malaria
Botulism Meningitis
Campylobacteriosis Mononucleosis
Cholera Pelvic Inflammatory
Disease
Ebola
Plague
Encephalitis
Polio
Escherichia coli
Infections Salmonella
Gonorrhea SARS
Hepatitis Smallpox
Herpes Streptococcus
(Group A)
HIV/AIDS
Staphylococcus
Human Papillomavirus
aureus Infections
and Warts
Syphilis
Influenza
Toxic Shock
Leprosy
Syndrome
Lyme Disease
Tuberculosis
Mad Cow Disease
Typhoid Fever
(Bovine Spongiform
Encephalopathy) West Nile Virus
 LEPROSY

Alfica Sehgal
FOUNDING EDITOR
The Late I. Edward Alcamo
Distinguished Teaching Professor of Microbiology,
SUNY Farmingdale

FOREWORD BY
David Heymann
World Health Organization
CHELSEA HOUSE PUBLISHERS
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©2006 by Chelsea House Publishers,

a subsidiary of Haights Cross Communications.
All rights reserved. Printed and bound in the United States of America.

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First Printing

1 3 5 7 9 8 6 4 2

Library of Congress Cataloging-in-Publication Data

Sehgal, Alfica.
Leprosy/Alfica Sehgal.
p. cm.—(Deadly diseases and epidemics)
Includes bibliographical references and index.
ISBN 0-7910-8502-3
1. Leprosy. I. Title. II. Series.
RC154.S38 2005
614.5'46—dc22
2005010391

All links and web addresses were checked and verified to be correct at the time
of publication. Because of the dynamic nature of the web, some addresses and
links may have changed since publication and may no longer be valid.
 Table of Contents
Foreword
David Heymann, World Health Organization 6
1. Historical Overview 8

2. The Spread, Signs, and Types of Leprosy 21

3. Leprosy Around the World 31

4. What Causes Leprosy? 35

5. Host-pathogen Interactions 45

6. Controlling the Disease 56

7. Understanding the M. leprae Bacillus 64

8. Ongoing Reforms and the Future 72

Glossary 78

Notes 81

Bibliography 82

Further Reading 83

Websites 84

Index 85
Foreword
In the 1960s, many of the infectious diseases that had terrorized
generations were tamed. After a century of advances, the leading
killers of Americans both young and old were being prevented with
new vaccines or cured with new medicines. The risk of death from
pneumonia, tuberculosis (TB), meningitis, influenza, whooping
cough, and diphtheria declined dramatically. New vaccines lifted the
fear that summer would bring polio, and a global campaign was
on the verge of eradicating smallpox worldwide. New pesticides
like DDT cleared mosquitoes from homes and fields, thus reducing
the incidence of malaria, which was present in the southern United
States and which remains a leading killer of children worldwide.
New technologies produced safe drinking water and removed the
risk of cholera and other water-borne diseases. Science seemed
unstoppable. Disease seemed destined to all but disappear.
But the euphoria of the 1960s has evaporated.
The microbes fought back. Those causing diseases like TB
and malaria evolved resistance to cheap and effective drugs. The
mosquito developed the ability to defuse pesticides. New diseases
emerged, including AIDS, Legionnaires, and Lyme disease. And
diseases which had not been seen in decades re-emerged, as the
hantavirus did in the Navajo Nation in 1993. Technology itself
actually created new health risks. The global transportation
network, for example, meant that diseases like West Nile virus
could spread beyond isolated regions and quickly become global
threats. Even modern public health protections sometimes failed,
as they did in 1993 in Milwaukee, Wisconsin, resulting in 400,000
cases of the digestive system illness cryptosporidiosis. And,
more recently, the threat from smallpox, a disease believed to be
completely eradicated, has returned along with other potential
bioterrorism weapons such as anthrax.
The lesson is that the fight against infectious diseases will
never end.
In our constant struggle against disease, we as individuals
have a weapon that does not require vaccines or drugs, and that
is the warehouse of knowledge. We learn from the history of sci-

6
ence that “modern” beliefs can be wrong. In this series of
books, for example, you will learn that diseases like syphilis
were once thought to be caused by eating potatoes. The inven-
tion of the microscope set science on the right path. There are
more positive lessons from history. For example, smallpox was
eliminated by vaccinating everyone who had come in contact
with an infected person. This “ring” approach to smallpox
control is still the preferred method for confronting an
outbreak, should the disease be intentionally reintroduced.
At the same time, we are constantly adding new drugs, new
vaccines, and new information to the warehouse. Recently, the
entire human genome was decoded. So too was the genome
of the parasite that causes malaria. Perhaps by looking at
the microbe and the victim through the lens of genetics
we will be able to discover new ways to fight malaria, which
remains the leading killer of children in many countries.
Because of advances in our understanding of such diseases
as AIDS, entire new classes of anti-retroviral drugs have
been developed. But resistance to all these drugs has already
been detected, so we know that AIDS drug development
must continue.
Education, experimentation, and the discoveries that
grow out of them are the best tools to protect health. Opening
this book may put you on the path of discovery. I hope so,
because new vaccines, new antibiotics, new technologies, and,
most importantly, new scientists are needed now more than
ever if we are to remain on the winning side of this struggle
against microbes.

David Heymann
Executive Director
Communicable Diseases Section
World Health Organization
Geneva, Switzerland

7
1
Historical Overview
“My life could have been so different and maybe a lot shorter” said Hari,
a young man from a rural village in India. He was found to have con-
tracted kushtha when he was only nine years old. As was often the case
with this disease, he was about to be abandoned by his family, until a very
open-minded doctor found out about him. Luckily, the boy did not have
a severely infective form of the disease and his family was not at risk. Still,
everyone in his village was too frightened to touch him. They called him
cursed and wanted nothing to do with him. They only knew that some-
thing terrible was making people in their village very ill. Fortunately, the
doctor succeeded in allaying the villagers’ fears, and, after many sessions
and conversations with almost half of the villagers, the boy was able to
remain with his family. He was properly treated, and soon, the only
reminder of the disease we know as leprosy was a tiny scar on his
back. Listening to this young man of 20, today, it is obvious that, in
addition to its physical symptoms, the disease also brought the devastat-
ing pain of social stigma. The fear of being left alone also had a positive
effect, however. It helped him to become a social worker, which is a
matter of pride for him today. He has been teaching biology in a school
for several years, and his own life experience has certainly helped him
reach out to his students.
Kushtha, the name by which leprosy, or Hansen’s disease, is known in
India, is also the name used to document the disease in very early scrip-
tures of ancient Indian civilization. No matter what it is called, leprosy is
caused by a bacterium called Mycobacterium leprae, a microscopic
germ, which is closely related to the tuberculosis bacillus. Like tuber-
culosis, it is transmitted through breathing—through droplets emitted by

8
a person with an active case of the disease. Unlike tuberculosis,
however, it is not highly contagious. Most people (90–95%) have
a genetic immunity to leprosy, and leprosy experts generally say
that prolonged and intimate contact with a contagious individ-
ual is required for a susceptible person to acquire the disease.
The disease principally affects nerves and skin, with
other organs of the body being affected only in late stages.
Germs may be spread through coughing and sneezing. Many
patients develop deformities due to nerve damage, as the
disease runs its course. Contrary to popular misconceptions,
leprosy does not cause limbs to fall off or flesh to rot. The
bacillus does, however, damage the peripheral nerves, causing
insensitivity or lack of feeling. Nerve damage is the major
cause of disability associated with leprosy. The painlessness
that results from nerve damage allows affected individuals
to ignore cuts, burns, and other injuries sustained during
everyday activities. These injuries may become infected or
even gangrenous, and amputation is required in some cases.
As a result of these deformities, patients are often isolated,
affecting their social and economic well-being. According to a
statistics in 1991 an estimated 6 million people worldwide are
infected with leprosy.
Until the discovery of AIDS (acquired immune deficiency
syndrome), leprosy was the most feared infectious disease in
the world. Even today, however, leprosy’s effects still drastically
change the lives of millions of people—living mainly in Asia,
South America, and Africa. Brazil is the second-most affected
nation, after India.
In the last half of the 14th century, leprosy swept
though Europe, killing one-third of the population, but it
came and went quickly, like a great earthquake, followed by
a series of aftershocks. Today, the disease is most prevalent
in underprivileged areas, where crowded and unsanitary
conditions contribute to its spread. Leprosy has even been
known to develop in more developed nations, from time to

9
10 LEPROSY

time. In the United States, the disease is found mainly

in Louisiana, Texas, Florida, Hawaii, and California. It
can also be found in the Northeast, however, and other
areas where immigrants from endemic areas have settled.

LEPROSY: THE HIDDEN DISEASE

When the rash on his chest first appeared, the 48-year-old
office worker dismissed it as an allergic reaction to the shell-
fish he had recently eaten. His doctor agreed and prescribed
an ointment. But when the red bumps did not go away after
several months and began to spread to his legs, arms, and
face, the man began to worry. He saw another doctor, who
had no explanation for his condition, and finally another,
who gave him a startling diagnosis: leprosy.
In the United States, leprosy is usually regarded as a
plague of the past, a disease relegated to biblical times or,
perhaps, to poor and distant countries. In fact, as cases of
leprosy have been declining worldwide in recent years, the
infection has actually been on the rise in the United States.
While there were some 900 recorded cases in the United
States 40 years ago, today more than 7,000 people have
leprosy, or Hansen’s disease, as it is now called.
The disease, even with its sanitized name, can still
confer pariah status on the victim. Thus, there is no sign on
the door announcing a clinic in New York, even though it
has almost 500 people receiving regular outpatient care and
is one of only 11 federal Hansen’s disease centers. On a
recent morning, a sampling of patients, all of them wishing
to remain anonymous, said they were loath to tell others
about their diagnoses.
A Queens, New York, man tells his friends that the
bumpy patches on his arms are allergies, and a stylish
college student has kept her infection secret from every-
one but her grandmother. A 61-year-old Staten Island
 Historical Overview 11

Although, there is an effective treatment for the disease, the

number of cases in the United States is still significant. The
World Health Organization (WHO) is working to eradicate
the disease worldwide.

man who is being treated for a recurrence of leprosy he

first contracted 40 years ago says he still has not told his
wife of 33 years.
Most of those infected in the United States are immigrants
from global leprosy hot spots—Brazil, India, and the Caribbean,
for example. In the past six years, however, a few patients at
the New York clinic—including a 73-year-old man from Queens,
who had never been out of the country, and an elderly Jewish
man from Westchester County—have contracted leprosy in
the United States.
As a result, the disease is now officially endemic to the
Northeastern United States for the first time ever. (Cases of
leprosy transmission in the Southeast date as far back as the
turn of the 19th century.) Leprosy experts think that even some
foreign-born people with the infection may have acquired it in
immigrant communities here.
Leprosy’s symptoms—bumpy rashes, skin indentations,
and loss of feeling in hands and feet—are often misdiagnosed
as being caused by a variety of disorders, including bug bites
and lupus. Promptly recognized, the disease is relatively
easy to treat. With a standard regimen of multiple drugs, a
vast majority of people with leprosy cease to be contagious
within three months and become free of the bacteria that
cause it in two to five years. Without treatment, however,
the disease can be spread. The bacteria are thought to be
passed through the respiratory droplets of an infected person.
Untreated infections can also result in serious complications,
including the loss of toes or limbs.
12 LEPROSY

Leprosy is also known as Hansen’s disease, after Gerhard

Armauer Hansen, the Norwegian scientist who first observed
the bacillus under a microscope in 1873, and identified it
as the cause of leprosy. The disease shares a unique history
with human beings, because, unlike most communicable
diseases, Mycobacterium leprae has virtually only one host—
the human body.

HISTORY OF THE DISEASE

Leprosy has affected humans since the dawn of history, leaving
lasting imprints on religion, literature, and the arts. It is a
deep-rooted part of the human psyche, with both mystical and
physical meanings. Asians and Africans call it “the big disease,”
because of the damage it does to the soul and body of the
patient (Figure 1.1).
Leprosy appears in the Old Testament of the Bible (as the
Hebrew word tzaraath) and it probably covered a whole range
of horrible skin conditions, just as the Greek word lepra did in
the New Testament, where the words leprous or leprosy appear
54 times. These biblical accounts resulted in the disease being
linked to corruption of both the spirit and the body. The book
of Leviticus paints a chilling image of this disease: “And the
leper in whom the plague is, his clothes shall be rent, and the
hair of his head shall go loose, and he shall cover his upper lip,
and shall cry, unclean, unclean. And all the days wherein the
plague is in him he shall be unclean; he is unclean: he shall
dwell alone; without the camp shall his dwelling be.” 1
The Bible equated leprosy with sin. The disease was seen as
a punishment from God, for some transgression. According to
the Old Testament, Uzziah, the king of Judah, wanted to burn
incense in the temple of Jehovah, a ceremony reserved for
priests. The priests opposed him, and, the story goes, Uzziah
became angry, so God struck him with leprosy. King Uzziah,
was a leper until the day of his death, and dwelt in a separate
house. He was cut off from the house of Jehovah. The priests
 Historical Overview 13

did not drive Uzziah into the wilderness, like lesser sinners.
Instead, they stripped him of power and denied him burial
in the cemetery of kings. The New Testament treats lepers

ARMAUER HANSEN AND

THE DISCOVERY OF LEPROSY
A prominent dermatologist in Norway, Daniel Cornelius
Danielsen, wrote the first extensive description of leprosy
in 1847; it was this description that Norwegian physician
Armauer Hansen used 20 years later as the basis for his
studies of leprosy. Up to this time, researchers had been
unable to infect laboratory animals with the disease, nor
were they able to grow the bacteria in culture. Still unsure
what caused leprosy, Hansen undertook a bold approach to
uncovering what caused the disease: He took tissue samples
from people infected with leprosy and implanted this tissue
into healthy nurses, patients, and other individuals. Hansen’s
experiments did not result in any healthy individuals becoming
sick, but they did result in harsh legal condemnation for
the maverick research physician.
Nevertheless, Hansen remained committed to discovering
the cause of the dreaded disease and, in 1873, succeeded
in isolating and identifying Mycobacterium leprae under
the microscope (eight years before Koch successfully
isolated and identified the bacterium that causes human
tuberculosis). Hansen garnered the recognition he so
deserved in 1909, when he was honored at the Second
International Leprosy Congress in Bergen, Norway. Today,
Hansen’s name endures through the Armauer Hansen
Research Institute in Ethiopia, which is committed to
eradicating and treating leprosy and also to educating
leprosy field specialists.
14 LEPROSY

Figure 1.1 These ancient masks show the deformities that many
ancient cultures had associated with leprosy. Having leprosy
caused a person to be isolated and shunned from the community.

more kindly, but still sets them apart from other sufferers.
Jesus healed the blind and deaf, but cleansed the lepers,
implying that there was some moral stigma associated with the
disease. In biblical literature, segregation and disinfection were
 Historical Overview 15

mentioned as methods to contain the disease. The one thing

that we know for sure about leprosy is that it is a very old
disease, spanning back to biblical times.
One account of a disease that could be leprosy appears
in an Egyptian papyrus inscribed about 1552–1350 B.C.E.,
but no one really knows for sure whether the disease being
described was actually leprosy. Examination of mummies
in Egypt indicates that the disease existed in that country
as early as the 2nd century B. C . E . It is believed that, in the

SPECIAL MASS
There was a special mass performed in the Middle Ages in
Western Europe, at the site of a newly identified leper’s hut.
Sometimes referred to as a Mass of Separation, one such
version of the mass as spoken by the priest is as follows:

I forbid you to enter the church or monastery, fair, mill,

market-place, or company of persons...ever to leave
your house without your leper’s costume [a white robe
to cover the body] and a bell in hand...to wash your
hands or anything about you in the stream or fountain.
I forbid you to enter a tavern...I forbid you, if you go on
the road and you meet some person who speaks to you,
to fail to put yourself downwind before you answer...I
forbid you to go into a narrow lane so that if you should
meet anyone he might catch the affliction from you...I
forbid you ever to touch children or give them any-
thing. I forbid you to eat or drink from any dishes but
your own. I forbid you to eat or drink in company,
unless with lepers.*

Ignorance about the disease led people to associate it with

sins and dirt. Thus, separation of the patients from the rest of
society seemed the only logical choice.
* Acta Leprol., 2001 12:79–84.
16 LEPROSY

1st century B.C.E., following fighting in Egypt, Roman soldiers

of the army of Pompey, carried the disease with them when
they traveled from Egypt to Italy. It is also thought that, in
the Middle Ages, the disease spread from Italy, throughout
the rest of Europe.
The disease took on epidemic proportions in the 13th
century, during the Crusades. Advancing troops and pilgrims
are believed to have spread the disease, even to Jerusalem,
where King Baudouin is reported to have suffered from leprosy.
The disease has never been geographically localized to any one
particular area of the world, as evidenced by the fact that it
probably existed in India and in Japan before 1000 B.C.E.
Leprosy is mentioned (as kushtha) by the renowned
Indian physician, Sushruta, in his book Sushruta Samhita as
early as 600 B.C.E. There is some doubt, however, whether
kushtha meant leprosy, as we know it today. The disease also
appears in the records of ancient Greece, when the army of
Alexander the Great returned from India, in 326 B.C.E. In
Rome, the first mention coincides with the return of Pompey’s
troops from Asia Minor in 62 B.C.E. Asia, therefore, could have
been the cradle of infection, before it spread throughout most
of Europe.
During the Middle Ages in Europe, patients were segre-
gated into thousands of centers, which came to be known
as lazarets or leprosarias. As mentioned earlier, containment
was naturally considered the most practical means of control-
ling the disease. Leprosy came to be referred to as “the living
death” and its victims were actually treated as though they
had already died. Funeral services were conducted to declare
their “death” to society. Psychologically, victims of untreated
leprosy could actually develop a self-loathing, where they
imagined that, at heart, they were unclean and under some
sort of curse. Other cruel practices required the leprosy patient
to walk on a particular side of the road, depending which way
the wind was blowing. In some areas in Europe, people with
 Historical Overview 17

the disease were required by law to dress in special clothing,

wear a declaration sign around their neck, and ring a warning
bell announcing that they were “lepers,” and people should
flee. Other equally discriminating laws of church and state
required the use of separate seats in churches, separate holy
water vessels, and, in some cases in Britain, there was a
“lepers’ slot” in the church wall through which the “leper”
could view the communion service, but not “contaminate” the
service by his presence.
Around the end of the 15th century, leprosy ceased to be
endemic, with the exception of Norway and the Mediterranean.
It seems certain, however, that Spanish conquerors in the slave
trade, together with French-speaking colonialists who were
forced out of Nova Scotia in the middle of the 18th century, to
settle in the southern United States, helped to spread M. leprae
to the American continent. From Europe, in the early part of the
20th century, the European colonialists seem to have taken the
disease to certain islands in the Pacific Ocean, particularly
Nauru, in the southwestern Pacific Ocean, about 2,580 miles
(4,160 km) southwest of Hawaii.2

ATTEMPTS TOWARD DEVELOPING REMEDIES

In ancient times, containment was thought the only way to
eventually find a cure, but as human minds developed over
time, people started to think of other curative measures, as
well. Finding a cure became even more important when the
infected person was of significant stature in the community.
In Burma, according to legend, when the king of Burma
contracted leprosy, he was advised by the gods to eat the
fruit from the Kalaw tree, which was said to have cured him.
In reality, chaulmoogra oil extracted from the nut of this
particular tree had been used as a treatment for centuries,
with little real success.
For centuries, leprosy continued to take its toll in India,
and many patients were banished and sometimes killed. In
18 LEPROSY

Hindu mythology, the god Rama is said to have contracted

kushtha, but was cured by taking a medicine made from the
fruit of the chaulmoogra tree. The same fruit was rumored to
have been effective in China.
In 1853, Dr. J.F. Mouat, of the Bengal Medical Service was
presented with a drunken, filthy beggar, who obviously had
kushtha. Mouat remembered the famous Hindu epic about
the god Rama being cured by the fruit of the chaulmoogra
tree and had an interest in Indian herbal medicines, so he
decided to administer the crushed chaulmoogra seeds six
times a day to the sick man. He was so impressed by the
improvement in the beggar’s health, that he wrote an article
of his trials for the Indian Medical Journal. He also shared
some of the oil with medical colleagues serving in Mauritius.
News of the value of this oil, sometimes also called hydno-
carpus oil, spread throughout the world, and experiments
were also carried out in Egypt to test its effectiveness against
the M. leprae bacterium.
Around the same time, an Irish adventurer named
Wellesley Bailey, traveled to Australia and New Zealand, in a
futile search for gold and a fortune in farming. He eventually
found his way to India, where he planned to join the police
force in Faizabad, in what is now Uttar Pradesh, in the north-
ern part of India. The police force, however, did not hold his
interest for long and he drifted into missionary service. The
American Presbyterian Mission appointed him as a teacher in
one of its schools in northwest India. He was later appointed
as a volunteer to take care of lepers. He wrote, “If there
was ever a Christ-like work in the world, it is to go amongst
these poor sufferers and bring them the consolation of
the Gospel.” 3
Wellesley Bailey’s girlfriend, Alice Grahame, lived in
Dublin and shared with her friends—the three Pim sisters,
Isabella, Charlotte, and Jan—some of her letters from Wellesley.
The letters told of the terrible suffering of those with leprosy.
 Historical Overview 19

Wellesley and Alice were married in Bombay and continued

their missionary work for many years. The Baileys eventually
resigned from missionary service and returned to Ireland
where, in 1874, something occurred that would have wonder-
ful repercussions for leprosy patients in India.
The three Pim sisters were so shocked and moved by the
stories recounted in Wellesley’s letters, that they resolved to
produce an informational booklet containing 16 chapters,
entitled Lepers in India. This meager first step led to the
formation of The Mission to Lepers, later to be named The
Leprosy Mission, a pioneer organization for modern leprosy
work in India.
One year earlier, in 1873, Dr. Armauer Hansen, a Norwegian
scientist had discovered the cause of leprosy. At the time, many
thought leprosy was a “curse of God,” but Hansen demon-
strated that a bacterium—Mycobacterium leprae—which was
spreading in a frightening manner in Norway, was the real
culprit (Figure 1.2). In 1875, the Baileys returned to India. This
time, Wellesley Bailey was a lay-missionary, employed by the
Church of Scotland. Sadly, the mission refused to accept the
Baileys’ ministry to lepers as part of the Gospel. The Baileys left
the Church of Scotland Mission to more fully establish The
Mission to Lepers. Today, this same mission, renamed Leprosy
Mission International, is one of the largest agencies treating
leprosy patients in 30 countries—with over 100 hospitals-
clinics in India alone.
With the 1898 Leper Act, issued by the British govern-
ment in India, “lepers” were treated like animals, condemned
to suffer compulsory segregation in asylums or “leper
colonies.” The Mission to Lepers offered loving, compassion-
ate care at Purulia, West Bengal, where, later, the mission’s
headquarters for all of India and Southern Asia was estab-
lished. By the end of the 17th century, over 600 lepers were
accommodated at Purulia, where the mission provided free
education, comfortable living quarters, and limited medical
20 LEPROSY

Figure 1.2 Dr. Armauer Hansen, shown here, discovered

that leprosy was caused by the bacterium Mycobacterium
leprae. Leprosy is also known as Hansen’s disease after
Dr. Hansen.

and surgical treatment. (At the time, chaulmoogra oil was

the only drug available.)
Fortunately, the situation improved, somewhat. With
developing scientific knowledge and technological abilities,
things began to change for the better. Just how and when things
changed will be described in greater detail in Chapter 6.
 2
The Spread, Signs,
and Types of Leprosy
As we learned in Chapter 1, leprosy can have devastating physical
and psychological effects. Since biblical times, it has been one of
the most feared and socially stigmatizing diseases in the world. To
contract the disease, one has to live in close contact with an infected
individual for a prolonged period. That said, in 2002, 763,917 new
cases of leprosy were detected worldwide. It is, therefore, extremely
important to recognize the early symptoms of leprosy, report them to
medical authorities, start medication, and continue with treatment,
once diagnosed. Many people all over the world remain undiagnosed
or do not complete treatment, once they are diagnosed. Here is an
example to elaborate on this problem:
In September 1999, Standwa Jama was diagnosed with leprosy. At the
time, he was 12 years old. Standwa lived in the Eastern Cape Province of
South Africa. The Leprosy Mission had been running a leprosy control
program in the Eastern Cape, since 1981. Previously, there had been two
leprosy hospitals in the province, but they were closed, as treatment began
to focus more on home-based care and drug therapy (See Chapter 6).
Standwa was found by The Leprosy Mission’s program manager, Frikkie
Naudé. According to Naudé’s diagnosis, Standwa was suffering from
multi-bacillary leprosy. Standwa came from a very poor family and was
under the care of his aunt at the time of his diagnosis. He had never been
to school and was herding the family’s cattle. At first, Standwa was very
frightened of Naudé and his medical team, but Naudé eventually managed
to win his trust, and they developed a friendly relationship.

21
22 LEPROSY

Unfortunately, Standwa’s father came and took him away

to the city about 1,000 kilometers (621 miles) away. Appar-
ently, the father had found a small job for his son—and in a
poor family, any income was a blessing. In the meantime,
Standwa’s illness would not be treated. Naudé and his team
eventually found four other members of the family, who were
also suffering from leprosy. Altogether, five members of the
family were infected. Standwa’s brother, Xolani, had leprosy,
as did three of his cousins and his grandmother. Xolani was
diagnosed in May 2001. At that time, Standwa reappeared at
home and was able to resume treatment. At the time of his
diagnosis, Xolani was being taunted by other children because
of his swollen lips and nose. Swollen and flabby lips and facial
parts are among the definitive signs of the disease. Being
embarrassed by his disfigured face, Xolani had become socially
aloof. He used to avoid mixing and playing with other children
or interacting with anyone around till the treatment helped in
his recovery. All five of the family members are now receiving
treatment and returning to their normal live.

HOW IS THE DISEASE TRANSMITTED?

Throughout history, leprosy has been regarded as contagious
and those affected have been secluded and barred from society.
People feared that merely touching an infected person could
spread the disease. Today, scientists know that leprosy is not so
easily transmitted, but the exact mechanism of transmission of
M. leprae is still a mystery.
There are, however, theories about the possible ways the
disease is spread, including direct person-to-person contact, or
contact with respiratory secretions from infected individuals.
When an infected but untreated person sneezes, their nasal
secretions may contain large numbers of leprosy bacteria.
Conceivably, these released bacteria can be inhaled by a healthy
individual or could invade a healthy person’s body through a
cut or abrasion on the skin, infecting that person. There is some
 The Spread, Signs, and Types of Leprosy 23

evidence that contact with infected soil may also be a method

of transmission. It is important to note that most people will
never develop the disease, even if they are exposed to the
bacteria. In fact, 95% of the world population is immune to
the bacteria that cause leprosy. Although the exact reasons for
these differences are not completely understood, bad nutrition,
unhygienic habits, constitutional conditions (tuberculosis,
alcoholism) seem to favor its production and propagation.
Unlike other contagious diseases, such as influenza and
cholera, patients who receive treatment for leprosy do not
generally spread the disease, once treated. When a person with
leprosy is placed on medication, most of the bacteria in their
body dies off within a few days. Within a couple of weeks after
starting the medicine, the risk of transferring the disease is
negligible. Today, doctors believe that it is not necessary to
isolate a person with leprosy after the medical treatment has
begun. It is also important to note that the disease is not
transmitted sexually or from a pregnant mother to her fetus.
Very rarely do healthcare workers who care for patients
with leprosy develop the disease. The well-known case of
Father Damien, a Belgian missionary who contracted the
disease while caring for leprosy patients on the Hawaiian island
of Molokai, during the late 1800s, appears to be the exception,
rather than the rule (Figure 2.1).

SIGNS AND SYMPTOMS OF LEPROSY

Like most other diseases, early recognition or detection of
leprosy is very important. Early treatment can limit damage
caused by the disease, render the person noninfectious, and
allow the patient to lead a normal life. The most common first
sign is usually a spot on the skin that may be slightly red,
darker, or hypopigmented (lighter in color than the rest of the
skin). The spot often develops anaesthesia (loss of sensation)
and may lose hair. Some of these spots may slowly increase in
size and new spots may appear on other parts of the body. Most
24 LEPROSY

Figure 2.1 Father Damien was a Belgian missionary who worked

with leprosy patients on the Hawaiian island of Molokai. He is
seen here standing in front of his church with the patients that
he treated. Father Damien contracted leprosy and eventually
died of the disease.

often, spots appear on the arms, legs, or back. Skin lesions

that do not heal within several weeks of an injury are a typical
sign of leprosy. The order in which symptoms appear in a
particular body part is not completely understood.
As the disease progresses, patients can develop enlarged
peripheral nerves, usually near joints, such as the wrist, elbow,
and knees. Next, nerves in different body parts start to be
affected. If the arms are the infected limbs, part of the hand can
 The Spread, Signs, and Types of Leprosy 25

become numb and small muscles can become paralyzed, lead-

ing to the curling of the fingers and thumb (Figure 2.2). When
the disease attacks the nervous system in the legs, it interrupts
sensation in the feet. If facial nerves are affected, a person loses
the blinking reflex of the eyes, which can eventually lead to
dryness, ulceration, and blindness. Bacilli entering the mucous
lining of the nose can lead to internal damage and scarring

FATHER DAMIEN
Father Damien lived from 1840 to 1889, and was originally
named Joseph Damien de Veuster. He was one of Hawaii’s
most illustrious citizens. A Belgian missionary priest, he went
to Hawaii in 1864, as a Picpus Father (priest of the Sacred
Heart of Jesus and Mary). He was ordained in Honolulu and
worked among the islanders for several years. In 1873, at his
request, he was sent to the lepers’ colony of Kalaupapa on
the island of Molokai. There, he labored until his death from
leprosy. A dedicated and driven man, Father Damien did
more than simply administer the faith. He built homes,
churches, and coffins; arranged for medical services and
funding from Honolulu, and became a parent to children
whose own parents had died. A statue of Father Damien,
created by artist Marisol Escobar, stands in Statuary Hall
in Washington, D.C.
Kalaupapa’s reputation as a leper colony is well known.
Leprosy is believed to have spread to Hawaii from China.
The first documented case of leprosy occurred in 1848. Its
rapid spread and unknown cure precipitated the urgent need
for complete and total isolation of its victims. Surrounded
on three sides by the Pacific Ocean and cut off from the
rest of Molokai by 1,600-foot (488-m) sea cliffs, Kalaupapa
provided the perfect isolated environment. In early 1866,
the first leprosy victims were shipped to Kalaupapa and
lived there for seven years before Father Damien arrived.
26 LEPROSY

Figure 2.2 The man in this picture is afflicted with leprosy,

which has damaged his hands and arms. Leprosy causes
white patches of skin and numbing of the nerves in the
body, which can lead to damage of the extremities such
as the fingers and toes.
 The Spread, Signs, and Types of Leprosy 27

that, in time, causes the nose to collapse. The muscles get

weaker, resulting in signs such as foot drop (the toe drags when
the foot is lifted to take a step). Muscle weakness, scars or lesions
on body, loss of sensation from any discolored spot on the skin,
and prolonged healing time for wounds are also indications
that someone may be infected with leprosy bacteria. What
makes the bacteria harm one body part over another is not
clearly understood. Infection appears to be the result of inter-
play between the bacteria and the body’s immune system.

DEFORMITIES AND LEPROSY

If the early signs go unnoticed and, thus, are not medicated,
leprosy symptoms will start to intensify. Left untreated, leprosy
can cause deformity, crippling, and blindness. Because the
bacteria attack nerve endings, the terminal body parts (hands
and feet) lose all sensations and cannot feel heat, touch,
or pain, and can be easily injured. Patients end up hurting
themselves—often severely—with fire, thorns, rocks, and even
hot coffee cups. Left unattended, these wounds can then get
further infected and cause tissue damage. Along with these
injuries, fingers and toes become shortened and deformed, as
the cartilage is absorbed into the body. Contrary to popular
belief, the disease does not cause body parts to “fall off.”
In many patients, a large proportion of ulcers originate under
callused or scarred skin. This callus, if not regularly removed,
builds up and forms a thick mass, some of which dehydrates
and becomes hard. On the sole of the foot, this may cause
excessive pressure in the deeper tissues while walking, resulting
in ulceration (Figure 2.3).

TYPES OF LEPROSY
Depending on the number of lesions and the number of bacil-
lus observed on a lesion smear, leprosy can be classified into
two groups: tuberculoid and lepromatous (also discussed in
Chapter 5).
28 LEPROSY

Figure 2.3 Leprosy can cause curling of the fingers as the

muscles become paralyzed. It can also cause lesions to form,
such as the one on the palm of this person’s hand.

Tuberculoid Leprosy (TT)

In this form of the disease, the skin lesions appear as light red
or purplish spots. Patients usually have one or a few (normally
fewer than five) hypopigmented lesions with well-defined
borders. Tuberculoid leprosy is the more benign type, even
though the nerves are affected, which leads to numbness
(usually of the extremities). This form affects the peripheral
 The Spread, Signs, and Types of Leprosy 29

nerves and, sometimes, the surrounding skin, on the face,

arms, legs, and buttocks. Sensory loss is frequently observed
around the lesions. Tuberculoid leprosy is also known as
paucibacillary leprosy. In this type, the nerve architecture is
destroyed and there can be formation of granulomas in nerves.
Granulomas (inflamed nodules caused by the infection) are
visible at the clinical level, as asymmetric nerve enlargement
near the skin lesion.

Lepromatous Leprosy
In this type, the skin lesions appear as yellow or brown nodules
(protuberances), which are penetrated by many blood vessels.
Usually, there are multiple, poorly defined, hypopigmented
areas that affect the mucous membranes of the eyes, nose, and
throat. Multiple papules (nodular elevations on the skin) can
appear. These are usually symmetrically distributed and tend
to infiltrate (penetrate) the skin. There is a general thickening
of the skin, especially on the face and ears. Patients with an
advanced form of this disease may lose eyelashes or eyebrows.
When someone suffers from disfiguring facial features, this
condition is known as leonine facies. Lepromatous leprosy,
also called multibacillary leprosy, is the more easily spread of
the two forms of leprosy. This more severe form produces large
disfiguring nodules. The peripheral neuropathy (diseased state
of the nerves) observed in lepromatous leprosy, causes muscle
weakness and atrophy and has been associated with claw hands
and foot drops. In this form, the nerve structure is not
destroyed much, but the nodules present in the neural areas
have numerous bacteria.
According to some classifications, there is another form of
the disease, called borderline leprosy. This form is character-
ized by the presence of single or multiple skin lesions with
ill-defined or indistinct borders. Many satellite lesions emerge
around the larger ones. As suggested by the name, the nerve
structure shows an intermediate kind of pathology, with some
30 LEPROSY

Figure 2.4 Leprosy and its many forms can be classified in

several ways. The spectrum is illustrated here. Ridley and
Jopling suggest five forms, while the WHO suggests two
broader classifications.

damage, but not as much as is seen in the tuberculoid form.

This form can, however, cause maximum nerve damage, as
multiple nerves are involved. The nerve involvement is earlier
and faster than in the lepromatous form.
Different people have found more and more elaborate
ways to classify the disease and there are many intermediate
forms described between the tubercuolid and lepromatous
types. These forms are outlined in Figure 2.4.
 3
Leprosy Around the World
Leprosy is the oldest recorded disease in history, and it continues to be a
health challenge today. Prevalence of the disease has greatly decreased,
through the use of multi-drug therapy approved by the World Health
Organization (WHO) and vaccinations with BCG (Bacillus Calmette
Guérin) (discussed in Chapter 4). Though rare in the United States, the
disease is still a problem in parts of Texas and Louisiana, possibly due to
the presence of the nine-banded armadillo. Although the only known
reservoir for the bacteria that causes leprosy is humans, diseases caused
by bacilli indistinguishable from M. leprae have been discovered in
armadillos of the southern United States. There are approximately 7,000
people currently diagnosed with leprosy in the United States, and about
150 to 200 new cases are reported each year.4 The American Leprosy
Missions (ALM) helps to fund the U.S. Public Health Services’ National
Hansen’s Disease Program, located in Baton Rouge, Louisiana.
At the beginning of 2004, the number of leprosy patients under treat-
ment in the world was around 460,000. About 515,000 new cases were
detected during 2003. Among them, 43% were multibacillary cases, 12%
were in children, and 3% were diagnosed with severe disabilities. During
the previous two years, the global number of new cases detected had
continued to decrease dramatically (a reduction of about 20% per year).5
Information campaigns about leprosy in high-risk areas are crucial.
Patients and their families, who have historically been ostracized from
their communities, must be encouraged to come forward and receive
treatment (Figure 3.1).
The problem of accurate diagnosis is further complicated by the
inability to reach potentially infected areas. According to the WHO, there

31
32 LEPROSY

Figure 3.1 Global Leprosy Situation in 2004*

Point Cases detected

WHO Region Prevalence during year 2003

Africa 51,233 47,006

Americas 86,652 52,435

East Mediterranean 5,798 3,940

South East Asia 304,296 405,147

Western Pacific 10,449 6,190

WORLD 458,428 514,718

Figure 3.1 As of 2004, leprosy was most prevalent in South East

Asia according to the World Health Organization (WHO). Throughout
the world, there were over 400,000 cases of leprosy reported in
2004 alone. Most cases of leprosy are treatable, but people must
be informed about the disease and where to seek treatment.
* Adapted from www.who.int/en/

are approximately 3,000 cases of leprosy in the African nation

of Angola.6 The actual number of cases, however, is most likely
much higher. Inaccessible regions and land mines make accu-
rate reporting difficult in many areas of Angola. Poverty and
lack of education also contribute to the difficulty of properly
diagnosing affected patients. Angola has one doctor for every
16,152 people. (The United States, in contrast, has one doctor
for every 400 people) 7.
A similar example of inaccessibility to patients is seen in
the Philippines. According to the WHO, approximately 4,250
 Leprosy Around the World 33

cases of leprosy have been registered in the Philippines.8 Its

island geography, areas of high mountains, and deep jungles
make accurate recording difficult in remote regions. Remark-
ably, around 80,000 people have been cured with drug therapy
in the Philippines.9 Although there are many countries with a
relatively small incidence of the disease, the greater part of the
global burden is now focused on the top six endemic countries:
India, Brazil, Madagascar, Mozambique, Nepal, and Tanzania.
The total number of cases registered in these six countries
combined represents 83% of the global prevalence of the
disease. The prevalence rate is 3.4 cases per 10,000 people.
India alone represents around 64% of prevalence and 76% of
new cases in the world.10
We have certainly come a very long way from the first
International Leprosy Congress held in Berlin, Germany, in
1897. The only points on which all experts agreed at that time
were that leprosy was incurable, and that the only immediate
solution was to isolate patients. The first formal attempt
to estimate the global leprosy epidemic was made by the
WHO in 1966, resulting in an estimated total number of about
11 million cases, of which 60% of patients were not registered
for treatment.11 By the mid-1970s, it was obvious that efforts to
control leprosy with long-term Dapsone drug therapy were
failing. This realization led to the establishment of WHO/TDR
research programs directed at development of an effective
protective vaccine (known as IMMLEP) and more effective
leprosy therapy (known as THELEP).

LEPROSY IS DIFFERENT
Compared to many other infectious diseases, leprosy is very
different. This disease causes more pain and social trauma than
even death itself. When we look at the leading causes of death
worldwide: acute lower respiratory infection, tuberculosis,
diarrhea (including dysentery), HIV/AIDS, malaria, measles,
hepatitis B, pertussis (whooping cough), neonatal tetanus, and
34 LEPROSY

MODERN TECHNIQUES DETECT

LEPROSY IN ANCIENT SAMPLES
The human mind is always curious to know “when,” “where,”
and “how” things happen. In an attempt to understand the
spread of different diseases in ancient times, scientists have
devised many methods of study, at the molecular level. The
technique utilizes the unique features of the DNA of different
organisms. The molecular biology method used predominantly
for such experiments is called polymerase chain reaction
(PCR). People have been trying to analyze archaeological
material for the presence of pathogenic microorganisms like
Plasmodium (responsible for malaria), Schistosoma (a worm
causing schistosomasis), M. tuberculosis (causes tuberculosis),
and M. leprae (the leprosy bacteria). Results from some of these
experiments have demonstrated the presence of M. tuberculosis
DNA in specimens from the 18th century, and even earlier.
Some of this work was done using naturally mummified human
remains from the 18th century in Vác, Hungary. Analyses done
with samples from Dakhleh Oasis, Egypt (Roman period);
1st century Palestine; Poland and Hungary, dating from the
10th–11th centuries; and medieval Sweden show the presence
of M. leprae DNA in specimens.

dengue (hemorrhagic fever), we see that leprosy does not

even make the top ten. The issue with leprosy is not mortality
rates, but, rather, its social stigma. We need to look at leprosy
differently than we look at most other infectious diseases,
focusing more on instilling in the public an awareness of the
socially demoralizing aspect of the disease and its effects. With
leprosy, compassion and educated social values would do just
as much, if not more, than science and technology alone.
 4
What Causes Leprosy?
Bacteria are single-celled organisms without a defined nucleus that exist
all around us. They come in different shapes and sizes, occurring as
singles or in groups. Some bacteria form chains, while others are in groups.
These little creatures are an integrated part of our ecosystem, and they
serve many different roles. Their effects on our lives can be beneficial,
harmful, or neutral. Harmful bacteria can cause milk to spoil and old
vegetables or meats to decay. They can also cause a sore throat or a major
debilitating disease, like tuberculosis or leprosy. The bacteria responsible
for tuberculosis and leprosy are rod-shaped and are known as bacillus
or bacilli (plural). The round or spherical bacteria are called cocci and
these also include bacteria that can lead to sore throat (e.g. streptococcus
pyogens) (Figure 4.1). We do have some useful bacteria that live in our
food gut. These don’t harm us and can help in food digestion. Another
example of useful bacteria is Staphylococcus lactis. These bacteria are
responsible for formation of yogurt from milk.
With so many bacteria around us, how do we recognize them? How do
we distinguish one from another? Scientists have made various classifica-
tions, based upon different criteria. Bacteria can generally be divided into
two main groups: eubacteria (in Greek eu means “good”) or true bacteria,
and archaebacteria (in Greek archaios means “ancient”). These two types
of bacteria differ in many respects, including the composition of their
membranes, the type of ribosomes, and structure of their tRNA (transfer
RNA). Most of the bacteria we encounter in our daily lives are eubacteria.
For classification purposes, the kingdom of prokaryotes (organisms that
lack a true membrane bound nucleus) is further divided. Bacteria are
arranged into different classes, which are then subdivided into families.

35
36 LEPROSY

Figure 4.1 The bacteria that cause leprosy are rod shaped,
such as the bacteria seen in this micrograph, taken with a
scanning electron microscope and magnified 3,250 times
(top). Bacteria can also be round in shape, such as the
bacteria seen in the bottom picture (transmission electron
microscope, magnified 5,000 times).
 What Causes Leprosy? 37

Each family has many genera, and each genus can have many
species. As an example, Mycobacteria is a genus name. It
belongs to the family Mycobacteriaceae. This family belongs
to the class called Actinomycetales. The bacteria that causes
leprosy is called Mycobacterium leprae, with leprae being the
species name (Figure 4.2).

THE FAMILY OF MYCOBACTERIA

Many members of this group are free-living, but the group is
probably best known for its animal pathogens. M. bovis causes
tuberculosis in cattle, other ruminants, and primates. These
pathogens can also cause diseases in humans, so cattle are tested
routinely. The milk available for our consumption is generally
pasteurized before sale. Pasteurization kills all harmful living
pathogens, including Mycobacteria and prevents disease trans-
mission. A close relative of M. bovis is M. tuberculosis, which
causes tuberculosis in humans. M. avium, on the other hand,
is associated with pneumonia in birds. Several other members
of the family of mycrobacteria are known to be opportunist
pathogens. They infect individuals who are weak, undernour-
ished, or have weak immune systems. Many of these opportunist
infections are found in AIDS patients.
Corynebacteria belong in the family Mycobacteriaceae and
are part of the CMN group (Corynebacteria, Mycobacteria, and
Nocardia). As a group, they produce long chain fatty acids called
mycolic acids (discussed in Chapter 5). For Corynebacteria,
chains of 28 to 40 carbons are common; for Nocardia, chains
of 40 to 56 carbons are produced; for Mycobacteria, the chains
are 60 to 90 carbons in length .

MYCOBACTERIUM LEPRAE
The Mycobacterium leprae bacillus, also known as Hansen’s
bacillus, ranges from 2 to 7 micrometers (1 micrometer
=1/1000 of a millimeter) in length and 0.3 to 0.4 micro-
meters in width. Like many other bacteria, M. leprae has
38 LEPROSY

Figure 4.2 Leprosy is caused by Mycobacterium leprae, a

rod-shaped bacterium. This sample was taken from a skin
lesion. Mycobacterium leprae are between 2–7 micrometers
in length.

four components: the capsule, the cell wall, the membrane,

and the contents of the cell (cytoplasm and nucleic acid)
(Figure 4.3). What makes it different from other bacteria is
 What Causes Leprosy? 39

its unique cell wall or cell coat. These Mycrobacteria have

a cell wall that is very rich in lipid (fats, oils) content, and
they contain waxes. The complex fatty acids and lipid
layer makes them acid-fast, or impenetrable to acids. The
bacteria do not follow the normal bacterial staining prin-
ciples and are resistant to treatment with an acid or alcohol.
M. leprae stains with the Zeihl-Neelsen staining method,
use carbol fuchsin, rather than with the traditional Gram
staining method. The Zeihl-Neelsen staining method
involves heating the bacterial smear on the slide with carbol
fuchsin for about five minutes.

TUBERCULOSIS
In 1882, Robert Koch identified the organism that causes
human tuberculosis (TB), Mycobacterium tuberculosis.
At the time, TB was rampant, causing one-seventh of all
deaths in Europe. Even today, the disease remains a global
health problem, with around 1 billion people (over 20% of the
world’s population) infected worldwide. In the United States,
the disease occurs most commonly among the elderly,
malnourished people, alcoholics, impoverished males, and
Native Americans. This bacterium is primarily transmitted
through contact with the nasal or oral secretions of the
infected patients.
Disease symptoms include fever, fatigue, and weight
loss. The disease is generally characterized by a persistent
cough. In many countries, individuals, especially infants, are
vaccinated against this bacteria by BCG (Bacilli Calmette
Guérin). The disease is preventable by maintaining better
public health standards and improving social conditions,
for example, reducing homelessness and drug abuse. Once
someone is infected, the disease can be fully cured under
supervised medical treatment, especially if detected in
early stages.
40 LEPROSY

Figure 4.3 Mycobacterium leprae, like many bacteria, have

a capsule, cell wall, and a membrane, which are illustrated
in this schematic of a basic bacterial cell. However, the
cell wall of the leprosy bacteria is different than many other
bacteria, making them difficult to test using traditional
staining methods.

THE CELL WALL

The bacterial cell wall is a semi-rigid, tight knit structure con-
taining peptidoglycan. The main function for the cell wall is
to prevent against osmotic lysis. These bacteria have a thick
 What Causes Leprosy? 41

wax-coated cell wall. The major component of this cell wall is

mycolic acid. In fact, it is the major component of the cell wall
of the taxa actinomycetes. Different genera belonging to this
class are Mycobacterium, Gordona, Nocardia, and Rhodococcus.
Mycolic acids are localized in the inner leaflet of the cell wall,
either covalently bound or loosely associated with polymers.
These mycolic acids are complex hydroxylated branched-
chain fatty acids, with 60 to 90 carbon molecules. Along with
hydroxyl (-OH) groups, they can further diversify with differ-
ent organic groups, like methoxy (CH 3O) and keto (CO).
In 1938, these fatty acids were first isolated from a waxy
extract of human tubercle bacillus. Their common structure
was revealed in 1950 by J. Asselineau. Now, mycolic acid
forms a broad family of over 500 types. The mycolic acid
from Mycobacterium can be more complex, with a range of
functional groups, whereas other members may have simpler
forms with no extra chemical groups. For classification
purposes, the mycolic acids isolated from Mycobacterium are
called eumycolic acids (or just mycolic acid). The acids isolated
from Corynebacterium and Nocardia are named coryno-mycolic
and nocardo-mycolic acids, respectively.
Mycolic acids are responsible for maintaining a rigid
cell shape and may constitute up to 60% of the dry weight
of an organism. They also make the bacteria resistant to
chemical injury, thus protecting cells against hydrophobic
(hydro=water, phobic= hate or fear) antibiotics (Isoniazid,
which inhibits mycolic acid biosynthesis is an efficient
antimycobacterial agent.) It is because of this waxy coating
that the bacterium gains its hydrophobic characteristics.
While this resistant cell wall continues to pose challenges in
combating the microbe, paleobiologists, scientists who study
the biology of fossil organism, have found a use for it.
Because of the stable nature of the fatty acids, they can be
used to identify the type and extent of disease found in
ancient times. Paleo-epidemiologists, scientists who study
42 LEPROSY

disease in fossil organisms, can study fatty acids by analyzing

the ancient skeletons.

WHERE IS THE LEPROSY BACILLUS FOUND?

The most natural and congenial environment for M.leprae is a
eucaryotic cell, which, in most cases, is found in humans, but

HOW ARE BACTERIA COLORED?

Bacteria are among the smallest living organisms. They are single
celled and vary in size from 0.5 micrometer (mm) to 10 mm
(1mm=1/1000 cm). Imagine trying to see an object that is
100th the size of a sand particle. Because something so
small cannot be seen with an unaided eye, scientists use
microscopes. To make the visualization process easier and
more informative, scientists have developed techniques to
stain the bacteria, according to their composition, to help
in their identification. The most common method used for
bacterial staining is called Gram staining and was developed
by the Danish physician Christian Gram in 1884.
In a microbiology lab, this simple staining method
begins with applying bacteria to a slide. The slide is then
soaked in a violet dye followed by iodine treatment. The
slide is then rinsed with alcohol and counterstained with a
pink dye called safranine. This staining procedure divides
bacteria into two classes: gram-positive and gram-negative.
The cell walls of gram-negative bacteria have a very low
affinity for the violet stain, which is rinsed out by the alcohol.
Once counterstained with safranine, however, the gram-
negative bacteria appear bright pink or red. Gram-positive
cell walls have a high affinity for the violet stain, and
retain it, even through the alcohol rinse. When the process
is complete, they appear dark purple or brown. The difference
in composition of the bacterial cell walls leads to this
differential staining. Gram-positive cell walls are about
 What Causes Leprosy? 43

occasionally may be found in the nine-banded armadillo, the

mouse footpad and, to a lesser degree, the monkey. Scientists
have also been able to grow the majority of pathogenic
Mycobacteria in a variety of laboratory culture media, with the
help of various nutrients. M. leprae still cannot be cultivated
artificially in laboratory media, causing much frustration and

five times as rich in peptidoglycan as gram-negative cell

walls. Members of mycobacteria are unique in their cell wall
composition and do not stain by this universal standard method.
They are stained by a much harsher treatment that is also
used in their identification (Figure 4.4).

Figure 4.4 This micrograph (taken with a light microscope and

magnified 1,000 times) shows both gram-positive and gram-
negative bacteria. When stained with the Gram Stain technique,
gram-positive bacteria appear purple and gram-negative bacteria
appear pink or red.
44 LEPROSY

delay in finding an effective anti-leprosy vaccine, or a thorough

understanding of the bacteria.
The leprosy bacillus is an obligate intracellular parasite. It
is a slow growing bacteria that multiplies with a generation
time of 12.5 days. It grows best at 27–30°Celsius (80–86°
Fahrenheit), hence its predilection for cooler areas of the
human body (like finger tips).
 5
Host-pathogen
Interactions
Mycobacterium leprae attacks the host body as if it were a foreign invader.
As a natural response to any such invasion, the host system tries to defend
itself. First, it tries to prevent the invader from entering its system. Then, it
tries to kill and eliminate the invader, once it is inside. This host response
to pathogens is called the immune response. In short, the host tries to
mount an immune response against the parasite, and the pathogen’s
natural reaction is to evade it. Before we talk more about the specific
case of human response to Mycobacterium, let’s look at a bit of general
information about the immune system.

THE SYSTEM THAT PROTECTS US

The term immunity comes from the Latin expression immunitas,
meaning “freedom from.” Indeed, the immune system gives us freedom
from the attack of innumerable pathogenic organisms and their ill
effects. Every single organism needs some form of immunity, because
every single form of organism can be attacked by another. Even bacteria
have molecules that protect them from being hijacked by viruses.
Bacteria, on the contrary, are very clever and keep trying to fool our
immune system.
The ability of the immune system to mount a response to disease
is dependent on many complex interactions between the components of
the immune system and the antigens on the invading pathogens, or
disease-causing agents. We will learn more about the cells of the immune
system in the discussion that follows. Immunity in higher organisms, like

45
46 LEPROSY

vertebrates, can be divided into two major categories: innate

and acquired.

INNATE IMMUNITY
The innate or natural immune system is that part of the
immune system that we are born with. The innate immune
system keeps out invading organisms (pathogens), such as
viruses, bacteria, and fungi through a number of mechanisms.
These mechanisms include physical barriers, such as the
skin and the mucous layers; fever to overheat the invaders;
pathogen destroying enzymes secreted in mucous layers
and elsewhere; and acidic bodily secretions, which bacteria
do not like. Other mechanisms through which the immune
system keeps out invading bacteria include the comple-
ment—a system of plasma proteins that principally attack
bacteria; the inflammatory response, which involves the
action of several biochemicals and immune cells to destroy
pathogens, prepare other cells to resist attack, and regulate
downstream steps of the immune response; and non-
specific white blood cells, called effector cells, principally
the macrophages that gobble up pathogens. Innate immu-
nity is not specifically geared toward any particular kind of
organism. It is a nonspecific array of defense mechanisms
to prevent any organism from getting into or thriving in
our systems.

ACQUIRED IMMUNITY
Also known as specific or adaptive immunity, acquired immu-
nity focuses on those features of the immune system that are
“learned” during a person’s lifetime, rather than the immunity
an individual is born with. This part of the immune system
deals with specific invaders and learns to recognize them
by exposure to them. Acquired immunity can function at
different levels and in different forms, called humoral and
cell-mediated immunity.
 Host-pathogen Interactions 47

Humoral immunity principally operates through a type

of white blood cell called a B-cell, which originates in bone
marrow and the spleen. During humoral immune responses,
proteins called antibodies, which can stick to and destroy
antigens (any foreign molecule or organism which can elcit
an immune response by our body), appear in the blood and
other body fluids. These antibodies are produced specifically
against each organism. Humoral immune responses resist
invaders that act outside of cells, such as bacteria and toxins
(poisonous substances produced by living organisms).
Humoral immune responses can also prevent viruses from
entering cells (Figure 5.1).
Cell-mediated immunity operates through another type
of white blood cell called a T cell, which matures in the
thymus, (a small glandular organ located behind the breast-
bone). During cell-mediated immune responses, cells that can
destroy other cells become active. Their destructive activity is
limited to cells that are either infected with, or are producing,
a specific antigen. The T cell system first recognizes some
non-self molecules and then prepares its army against
these invaders. With a new set of cells that have new tools
(killer molecules), the T cells attack the infected body cells.
For the T cells to recognize the infected cell as a target,
the infected cell needs to look considerably different and
display some new kind of molecular appearance, on their
surface. Cell-mediated immune responses resist invaders
that reproduce within the body cells, such as viruses. Cell-
mediated responses may also destroy cells making mutated
(changed) forms of normal molecules, as is the case in
some cancers.

OTHER COMPONENTS OF THE IMMUNE SYSTEM

The immune system is very complex and there are some
more terms we need to understand before we understand
how “smart” the leprosy bacillus is.
48 LEPROSY

Figure 5.1 The body produces antibodies to attack foreign

molecules, called antigens, before they can cause harm. Antibodies
attach to the surface of an antigen, as is illustrated here, and
mark it to be destroyed by the body. This is one way that the
body fights disease.

Macrophages: White blood cells are the mainstay of

the immune system. Some white blood cells, known as
macrophages, play a function in innate immunity by surround-
ing, ingesting, and destroying invading bacteria and other
 Host-pathogen Interactions 49

foreign organisms in a process called phagocytosis (literally,

“cell eating”), which is part of the inflammatory reaction.
Macrophages also play an important role in adaptive immunity
in that they attach to invading antigens and deliver them to be
destroyed by other components of the adaptive immune system
(Figure 5.2).

Lymphocytes: Lymphocytes are specialized white blood cells

whose function is to identify and destroy invading antigens.
All lymphocytes begin as “stem cells” in the bone marrow, the
soft tissue that fills most bone cavities, but they mature in
two different places. Some lymphocytes mature in the bone
marrow and are called B lymphocytes. B lymphocytes, or
B cells, make antibodies, which circulate through the blood
and other body fluids, binding to antigens and helping to
destroy them in humoral immune responses.
Other lymphocytes, called T lymphocytes, or T cells,
mature in the thymus (as described in the previous section).
Some T lymphocytes, called cytotoxic (cell-poisoning) or killer
T lymphocytes, generate cell-mediated immune responses,
directly destroying cells that have specific antigens on their
surface, which are recognized by the killer T cells. Helper
T lymphocytes, a second kind of T lymphocyte, regulate the
immune system by controlling the strength and quality of all
immune responses.
Most contact between antigens and lymphocytes occurs
in the lymphoid organs—the lymph nodes, spleen, and
tonsils, as well as in specialized areas of the intestines and
lungs. Mature lymphocytes constantly travel through the
blood to the lymphoid organs and then back to the blood
again. This recirculation ensures that the body is continuously
monitored for invading substances.

Antigen receptors: One of the characteristics of adaptive

immunity is that it is specific. Each response is tailored to a
50 LEPROSY

Figure 5.2 Macrophages are a type of white blood cell that

destroy foreign invaders by swallowing them. The macrophage
in this picture has extended “arms” around the rod-shaped
bacteria and is attempting to clear the bacteria from the organism’s
body before they can cause harm.

specific type of invading antigen. Each lymphocyte, as it

matures, makes an antigen receptor—that is, a specific struc-
ture on its surface that can bind with a matching structure
on the antigen like a lock and key. Although lymphocytes can
make billions of different kinds of antigen receptors, each
individual lymphocyte makes only one kind of receptor. When
 Host-pathogen Interactions 51

an antigen enters the body, it activates only the lymphocytes

whose receptors match up with it.

Antigen presenting cells: When an antigen enters a cell,

certain transport molecules within the cell attach themselves
to the antigen and transport it to the surface of the cell, where
they “present” the antigen to T lymphocytes. These transport
molecules are made by a group of genes called the major histo-
compatibility complex (MHC) and are therefore known as MHC
molecules. Some MHC molecules, called class I MHC molecules,
present antigens to killer T cells; other MHC molecules, called
class II MHC molecules, present antigens to helper T cells.

FAVORITE TARGETS OF M. LEPRAE

Most pathogens prefer one kind of cell in our system to
another. Not all cells are the same. Not all of them provide
the best environment or food to the invading pathogen.
The M. leprae bacterium invades peripheral nerves and skin
cells and becomes an obligate intracellular parasite—that is,
it is a parasite that can live only in this environment. It is
most frequently found in the Schwann cells and mono
nuclear phagocytes (macrophages). The M. leprae shows a
strong affinity toward a protein called laminin, which is
specifically found in nerve tissues. That partially explains its
affinity toward Schwann cells. Macrophages are described as
the part of the “components of the immune system.”

WHAT HAPPENS WHEN M. LEPRAE

AND OUR BODY SEE EACH OTHER?
Because living M. leprae produce no toxins and no power of
locomotion, it is thought that they cannot enter unbroken skin
or intact mucous membranes. This issue, however, is still the
source of much debate. Most leprologists believe that M. leprae
can only enter through a break in the skin, and through the
mucous membrane of the nose, in particular.
52 LEPROSY

After M.leprae gain entry into the body, they can provoke
one of three possible, responses, contingent upon the measure
of cell-mediated immunity (CMI) in the host. To begin with,
they could be ingested by the macrophages and completely
digested, if CMI is present. This action can take place at the
point of entry or at the lymph nodes to where they may be
transported inside the large defense cells (macrophages). This
type of action is believed to take place in most people infected
by M.leprae, many of whom may never know they have been
invaded by the leprosy bacilli. Approximately 90 to 95% of
people exposed to leprosy experience this defensive action
of the body.
Second, in persons with no resistance (lack of CMI), M.leprae
freely multiply, even within the very cells (macrophage) that

SCHWANN CELLS
Various support cells are associated with neurons, most
typically, Schwann cells. A neuron is made up of a dendrite
that receives the impulse (from another nerve cell or from
a sensory organ), the cell body (numbers of which side-by-
side form gray matter) where the nucleus is found, and
the axon which carries the impulse away from the cell.
Wrapped around the axon are the Schwann cells, and the
spaces/junctions between Schwann cells are called nodes
of Ranvier. Collectively, the Schwann cells make up the
myelin sheath (numbers of which side-by-side form white
matter). Schwann cells wrap around the axon. Having an
intact myelin sheath and nodes of Ranvier are critical to
proper travel of the nerve impulse. Diseases that destroy
the myelin sheath (demyelinating disorders) can cause
paralysis or other problems. Schwann cells are analogous
to the insulation on electrical wires, and just as electrical
wires short out if there’s a problem with the insulation, so
too, can neurons malfunction when myelin sheaths are not
intact (Figure 5.3).
 Host-pathogen Interactions 53

are meant to destroy them. It is not uncommon for up to 300

M. leprae to proliferate inside these large defense cells, which
later transport the multiplying and dying (of old age) bacilli
from the site of entry to many different parts of the body. This
multiplication of the bacilli, even in the defense cells, is the
most serious—and contagious—form of leprosy, known as
lepromatous or multibacilliary (MB) leprosy.
Third, some patients have some resistance to the infecting
bacilli, but not enough immunity to completely destroy the
organisms. Their defense system allows a limited, but variable,
multiplication of the bacilli, contingent upon the degree of
CMI. In some patients—those with the tuberculoid form of
the disease—many of the bacilli are killed off by the body’s
defenses, which keep the infection localized to a small area of

Figure 5.3 Schwann cells help to insulate neurons, which

allow electrical impulses to travel down the axon at a faster
speed. The spaces between Schwann cells are called Nodes
of Ranvier.
54 LEPROSY

the body. In other patients, with a lesser degree of immunity,

the disease may be somewhat generalized, with leprosy lesions
scattered in different places. This form of the disease falls in
the “borderline” category. Borderline leprosy is immunolog-
ically unstable.
These groups constitute what is called the immunological
spectrum, ranging from those with a strong CMI at the tuber-
culoid end, to the more serious types, with a CMI deficit at the
lepromatous or infectious end. There is another group, which
is not considered as part of the spectrum. In its early stage, it
is not known whether it will progress into the spectrum to
become tuberculoid or lepromatous, so it is known as the
indeterminate form of the disease.

DAMAGE CAUSED BY INFECTION

The pathology associated with the disease is due to the body’s
immune response, rather than direct damage caused by the
bacteria. Most reactions are mainly observed during or after
multi-drug treatment (MDT). Leprosy reactions typically
represent acute inflammatory episodes of two major kinds:
erythema nodosum leprosum (ENL) or type II leprosy reac-
tions, and reversal reactions (RR) or type I reaction. ENL
occurs in patients with lepromatous leprosy and RR is seen
in patients with borderline leprosy. Lepromatous leprosy is
characterized by the absence of specific cellular immunity.
Therefore, there is uncontrolled proliferation of the bacilii with
many lesions and extensive infiltration of the skin and the
nerves. The dermis contains foamy macrophages filled with
many bacteria, but few mature T lymphocytes. Tuberculoid
leprosy patients have a vigorous cellular immune response
to the Mycobacterium, which limits the disease to a few well-
defined skin patches or nerve trunks. This type of reaction
generally leads to severe nerve damage.
Bacteria can directly or indirectly induce cell death or
apoptosis of the host Schwann cells. The presence of bacterial
 Host-pathogen Interactions 55

proteins in the nerve cell is recognized by the immune system.

Our cell-mediated immune system, involving T cells, tries to
rapidly detect invading pathogens and get rid of them, causing
the Schwann cells harboring the bacteria to be identified and
eliminated from the system. This causes removal of the impor-
tant nerve cells and debilitating neural damage. This process
also destroys nerve cells close to the infected Schwann cells,
resulting in large-scale nerve damage. Technically speaking,
reversal reactions are the primary cause of nerve damage.
6
Controlling
the Disease
When we experience physical discomfort, we are often told to see a
physician. But how does the physician know what is causing our pain and
how to cure it? Medical science has made many advances over the years,
and now has certain ways of assigning a symptom to a causative agent or
a known medical condition. This process is known as diagnosing a disease
or condition. Each ailment will have its own characteristic hallmarks or
symptoms, which distinguish it from other diseases. However, many signs
can be shared among several conditions—like fever, headache, and
fatigue. Medical science often plays a very important role in correctly
diagnosing an ailment and then treating the patient appropriately.

HOW IS LEPROSY DIAGNOSED?

Given the severely debilitating form the disease can take, early diagnosis
is essential. Unfortunately, this disease can superficially mimic many
dermatological and neurological conditions. The first signs of the disease
start with discoloration (change in normal color) of the skin. Certain
spots on the skin can become darker (hyperpigmented) or lighter
(hypopigmented). These spots also become anaesthetic (loose sense of
touch, heat, cold or pain). Such spots can appear anywhere on the body
and should be immediately reported to a physician. Other signs of the
disease include thickening of nerves and lesions in mucous membranes
(like in the nose). Anaesthetic skin or mucous membrane lesions in the
presence of enlarged nerves are also hallmarks of the disease. Primary
diagnosis is confirmed by taking samples from the skin. Smear biopsies

56
(small pieces of tissue) are taken from the skin and then
stained to detect bacteria. The density of bacteria observed is
recorded logarithmically, as the bacterial index (BI). Although
this test can confirm the presence of the disease, it does have a
limitation. If the amount of bacteria is too low, they will not
show up in the test.
In addition to microscopic detection, other methods are
used, as well. The most widely used serological test works by
detecting antibodies against the phenolic glycolipid-1 (PGL-1).
Antibodies are produced by our body against the bacterial
proteins, if there is an infection. These tests also have a
limitation. They can identify 90% of the severely infective or
lepromatous form of the disease, but only 40 to 50% of mildly
infective or paucibacillary patients.12 Such antibodies are
also found in 1 to 5% of healthy individuals living in infected
areas. Diagnosis using polymerase chain reaction (PCR) also
has similar limitations. It can diagnose 97% of multibacillary
patients, but only 44% of paucibacillary patients.13 PCR is only
useful clinically to support a diagnosis of leprosy when
atypical signs or characteristics are present. It was used to
detect the spread of disease in ancient times, as discussed in
Chapter 3. Ultimately, effective diagnosis in a person with
very low bacterial loads is still a challenge.

DRUG DEVELOPMENT
As we learned in Chapter 1, devising a proper curative treat-
ment for leprosy took time. Over many decades, and through
lots of trial and error, scientists eventually reached a situation
of greater confidence. Further study, in order to promote
greater understanding, is still ongoing, however.
Toward the end of 19th century (as is still true today),
this disease was still affecting more human lives in India than
anywhere else in the world. Initial attempts at drug therapy
were the result of early information about herbal therapy.
Meanwhile, research continued to improve on the chaulmoogra

57
58 LEPROSY

oil treatment, which was anything but the ideal therapy. Taken
orally, it produced nausea, while injections of the thick oil were
quite painful. In 1937, after a distinguished career, Wellesley
Bailey died, but not before seeing real hope for the patients he
had come to love and serve. Hope came in the form of the
discovery of one of the most revolutionary drugs of its day. As
early at 1908, German Chemist Gerhardt Domack had made
successful attempts to produce what eventually became the
parent chemical in the sulphone family of drugs. Out of this
research, evolved diamino diphenyl sulphone, (Dapsone, or
DDS), although at the time, no one associated DDS with a
possible cure for leprosy. It was considered too toxic a drug to
be used on humans. In 1941, American physician Dr. Faget was
courageous enough to use the parent sulphone drug, with
encouraging results (Figure 6.1).
Even then, as a bacteriostatic drug, DDS did not actually
kill the leprosy bacilli. It only prevented their multiplication.
For many years, it did seem that Dapsone would eventually
help in eliminating leprosy—that is, until resistant organisms
began to appear. Fortunately, new and more potent drugs, such
as Rifampicin, became available. Rifampicin, in combination
with other drugs (multi-drug therapy, or MDT), has given real
hope that, sometime in the future, the elimination of leprosy
could possibly become a reality. Rifampicin also kills the very
well-known cousin of M. leprae, M. tuberculosis. This drug acts
by stopping the synthesis of messenger RNA from DNA, by
affecting the enzyme (RNA polymerase) important for this
process (Figure 6.2). Rifampicin is specific to the bacterial
enzyme, and does not harm our enzyme function.
In 1981, the World Health Organization started recom-
mending multi-drug therapy. Three drugs are taken in combi-
nation: Dapsone, Rifampicin (or Rifampin), and Clofazimine.
Treatment takes anywhere from six months to a year or more,
depending on the extent and character of the disease. Multi-drug
treatment has brought new hope to millions of leprosy patients,
 Controlling the Disease 59

and, combined with more efficient means of diagnosis, has

resulted in the prevention of ulceration, crippling deformities,
and other disabilities. Multi-drug treatment helps to ensure that
a drug-resistant form of the leprosy bacterium will not develop.

NEW LEPROSY DRUG

Figure 6.1 In 1941, Dr. Guy Faget began administering the

first successful treatment for leprosy at the Carville Research
Center in Carville, Louisiana (shown above). The new sulfone
drug, Promin, proved successful in rendering leprosy patients
non-infectious. Today, several drugs are used in a multi-drug
fashion for 6 to 24 months to treat the disease.
60 LEPROSY

In addition, intensive health educational programs have

helped alleviate the misunderstandings and social stigma
often associated with the disease.
Leprosy treatment is not perfect, however. It can cause
severe side effects. These side effects are not the result of the
drugs themselves, but come instead as a result of inflammation
that develops when large numbers of leprosy bacteria are killed
and broken down inside the body. Freeing the body of dead
organisms is essential and can be accomplished by administer-
ing additional drugs to the patient. The inflammation must be
treated with anti-inflammatory drugs, such as corticosteroids,
to minimize additional nerve damage. Aspirin and prednisone
can also control inflammation, generally known as “erythema
nodosum leprosum” (ENL), which may occur with therapy.
Inflammation can cause fever, skin lesions, and other symp-
toms, which are thought to be a result of abnormal immune
reactions, against the killed bacteria (as they are still foreign to
our body).
Since the 1970s, studies have shown that ENL can be
effectively treated with the controversial drug known as
thalidomide. This drug does not attack the leprosy bacteria
directly, but helps to relieve the inflammation and heal the
skin sores in patients with ENL. In July 1998, the Food and
Drug Administration (FDA) approved thalidomide for the
treatment of ENL. The approval of thalidomide has been
queen controversial, however. In the early 1960s, the drug was
found to cause severe birth defects in thousands of babies
born in Europe, where thalidomide was often prescribed for
pregnant women suffering from morning sickness (Figure 6.3).
The drug, which was never approved in the United States, was
banned from pharmacies after it was linked to more than
10,000 infants born with shortened, flipper-like limbs and
other serious deformities.14
Leprosy can be avoided by covering the face and hands
when in the presence of infected individuals, and modern
 Controlling the Disease 61

Figure 6.2 Rifampicin is a new drug that is being used to

treat leprosy by inhibiting mRNA synthesis from DNA. During
normal DNA replication, mRNA is made from the DNA template
with the help of the enzyme RNA polymerase. However, Rifampicin
interferes with this process by binding to RNA polymerase and
preventing RNA synthesis.
62 LEPROSY

Figure 6.3 ENL, or erythema nodosum leprosum, can be treated

with the drug thalidomide. However, thalidomide is dangerous
for pregnant women, as it can cause severe birth defects such as
shortened or absent arms and legs. The baby in this picture suffers
from the effects of thalidomide.
 Controlling the Disease 63

antibiotics and new treatment regimens are helping to keep

the number of severely disfigured individuals to a minimum.
Killing bacilli (M. leprae) by multi-drug therapy is only one
measure of successful treatment for leprosy. Nerve damage,
leprosy’s hallmark symptom, is not reversed by MDT, however.
Many treated patients still need rehabilitation, while others
suffer from the enormous psychological stigma of the disease.
7
Understanding the
M. leprae Bacillus
Undoubtedly, for scientists to better understand a pathogen, that
pathogen needs to exist in large enough number to be studied. In essence,
scientists must understand the full strength of the “enemy,” before making
any attempt to manipulate it. Unfortunately, scientists are still struggling
with the leprosy bacillus, in this regard.
Most bacteria can normally be grown in a laboratory, in an artificial
setting. Free-living and non-pathogenic bacteria are easy to cultivate,
and can be grown in relatively simple media. This type of bacteria can
metabolize a mixture of protein, salt, and carbohydrates in order to grow.
They have all the metabolic pathways and enzymes to grow from basic
substrates. In fact, the ease of growing some of these bacteria and the
ability to manipulate them has provided biologists with a very useful tool.
The most commonly used bacteria in biological laboratories is a gram-
negative bacillus called Escherichia coli.
Unfortunately, growing pathogenic bacteria is not as easy. Many
parasitic bacteria need specialized medium to grow and divide. Examples
include blood agar, which is used to grow Lactococcus pneumoniae,
Staphylococcus aureus; and chocolate agar, which is used to culture
Haemophilus influenzae and Neisseria gonorrhoeae. Growing different
species of Mycobacteria has long been a challenge. Whereas some species
of Mycobacteria, like M. tuberculosis and M. bovis can be grown in vitro,
under special conditions, M. leprae has never been grown in artificial
media. It is an obligate intracellular pathogen, which means that it can
grow only inside a living cell and can never exist freely by itself. Because

64
the bacteria refuse to grow artificially, scientists must find
another way to study it.
Of course, one way to accomplish this is to isolate bacte-
ria from the patients and then use them for experiments.

E. coli
Escherichia coli (E. coli, for short) is a bacterium that
normally lives in the intestines of humans and other animals.
Most types of E. coli are harmless, but some can cause
disease. Disease-causing E. coli are grouped according to the
different ways by which they cause illness. Enterotoxigenic
Escherichia coli, or ETEC, is the name given to a group of
E. coli that produce special toxins which stimulate the
lining of the intestines causing them to secrete excessive
fluid, thus producing diarrhea.
The organism can be found on a small number of cattle
farms and can live in the intestines of healthy cattle. Meat
can become contaminated during slaughter, and organisms
can be thoroughly mixed into beef when it is ground. Bacteria
present on the cow’s udders or on equipment may get into
raw milk.
Eating meat, especially ground beef, which has not
been cooked sufficiently to kill E. coli, can cause infection.
Contaminated meat looks and smells normal. Although the
number of organisms required to cause disease is not known,
it is suspected to be very small. Among other known sources
of infection are consumption of sprouts, lettuce, salami,
unpasteurized milk and juice, and swimming in or drinking
sewage-contaminated water.
Bacteria in diarrheal stools of infected persons can be
passed from one person to another if hygiene or hand washing
habits are inadequate. This is particularly likely among toddlers
who are not toilet trained. Family members and playmates of
these children are at high risk of becoming infected.

65
66 LEPROSY

Although this approach is used for many experiments, the

number of bacteria available is limited, and very few studies
can be conducted. In addition, complications such as find-
ing patients and taking split-skin smears make this method
impractical. Further, there is also a chance of isolating
multiple types of bacteria from the same patient, thus
negatively affecting the results. Another method of experi-
mentation involves using some other animals as a host for
the M. leprae bacillus.
To a large extent, humans have been the only naturally
occurring host known for M. leprae, but that has changed.
Armadillos (Dasypus novemcintus) can also become infected
with the leprosy bacteria. This useful discovery allowed scien-
tists to bring armadillos into their laboratories to inject
them with the bacteria. The injected bacteria could cause
the disease and, at times, produce faster and more severe
symptoms than seen in humans. This realization provided
the researchers with a constant supply of bacteria to be used
for many more experiments.
In addition to armadillos, scientists have had some success
growing the bacteria in mouse footpads. Still, culturing them
takes a long time, as the bacteria divide very slowly, around
once every 15 to 20 days.

ARMADILLOS: THE ANIMAL OF CHOICE

Armadillos are not commonly used to grow the leprosy bacteria,
but, in addition to being able to grow the bacteria, they also
have other advantages. They are the only mammals known to
routinely give birth to quadruplets. Sometimes, embryos die
and triplets or twins are born, but the standard litter size for
armadillos is generally four identical pups. Derived from
single fertilized ovum, all four are the same sex and all contain
identical sets of genes, a major advantage for scientists seeking
to learn whether genetic predisposition plays a part in the
transmission of leprosy. No concrete documentation exists to
 Understanding the M. leprae Bacillus 67

link leprosy with any particular genetic makeup, but these

studies will be very informative. In addition, the armadillo
quadruplets are good test and control subjects for any experi-
ment. These football-sized mammals are tolerant of laboratory
procedures, unlikely to bite, and a have a large population, with
about 30 million in the United States alone (Figure 7.1).
The use of armadillos infected with leprosy has enabled
researchers to search for new drugs and to test whether older
drugs induce resistance after prolonged treatment. Similarly,
vaccine attempts depend upon the bacteria grown and isolated
from artificially infected armadillos.

THE AMAZING ARMADILLOS

The nine-banded armadillo, found in northern Argentina and
the southern United States, and a few close armadillo cousins
are found in South America. In general, armadillos are well
liked—and amusing. Homely, ungainly, and not too bright,
they epitomize the underdog and elicit our sympathy. Armadillo
festivals, races, comic books, T-shirts, and posters have swept
the South during the past decade. Texas jewelers have recently
advertised gold armadillo rings, pendants, and pins. Many
people eat armadillos and they are considered a delicacy in
parts of Mexico.
All armadillos in the United States vanished between
5,000 and 10,000 years ago, for unknown reasons. The many
thousands of nine-banded armadillos that now exist in Florida
are probably descendants of a fecund few that escaped from
captivity near Cocoa, Florida, only half a century ago. The
immigrant nine-banded armadillos from South America did
survive in Mexico, and from there, during the 19th century,
began one of the most rapid expansions in mammalian history.
They were first reported in southern Texas in 1854. Blocked
by the western deserts, they spread north to Kansas and
Missouri and east toward Florida.
68 LEPROSY

Figure 7.1 Armadillos are used for leprosy research. They

are suitable hosts to grow the leprosy bacteria and monitor
the disease. The hope is that by using armadillos as models,
scientists can find better and more effective treatments for
leprosy. The researcher in this picture holds an armadillo at
the Carville Leprosy Clinic in Carville, Louisiana.
 Understanding the M. leprae Bacillus 69

Of all the animals in the world, why would armadillos be

the preferred hosts for leprosy? From the previous chapters, we
know that the leprosy bacillus likes to stay in the cooler parts of
the body (nose, ears, finger tips, toes, scrotum). The armadillo’s
body temperature ranges from between 28 to 33° C (82.4 to
91.4° F) compared to 37° C (98.6° F) for humans.15 Leprosy
bacteria undoubtedly feel “at home” in armadillos. Armadillos
can live for 12 to 15 years in captivity, providing ample time to
develop advanced disease symptoms. It is interesting to note
that mouse footpads also have a lower temperature and are
cooler, thus also serving as a suitable habitat for M. leprae.
Armadillos in the wild can have leprosy, which creates a
concern about the ability of the disease spreading to people.
Thus far, however, very little evidence exists to suggest that the
disease can be transmitted in nature from armadillos to
humans. Although the hypothetical possibility of an endemic
always exists, the chances of it occurring are meager, at best.

GENOME SEQUENCING
We owe a lot to armadillos, with respect to our understanding
of the bacteria that causes leprosy. All organisms remain a
mystery, until we have deciphered their genes and functions,
at international levels, with help from many different groups,
scientists, and institutions. Scientists want to know about all
of the genes an organism has. This is achieved by genomic
sequencing (sequencing all DNA) from any organism in
question. Bioinformatics, the application of computer science
to the interpretation and management of biological data, has
provided many software programs and databases, which help
in quick, informative analyses of the obtained sequences. It is
important to know the DNA sequence, as the DNA holds all
the information about an organism—what it is, how it works,
and how it behaves.
Scientists have made a similar attempt to sequence M. leprae.
The bacteria for such a vast project were obtained from an
70 LEPROSY

armadillo-derived Indian isolate. The bacteria used was

isolated from India and grown in armadillos. The leprosy
bacterium has 3.27 Mb (mega base pair) genomes that have
been mapped. This genome size is much smaller than that of
its close relative M. tuberculosis, which has a genome size of
4.4 Mb. The genomic sequence revealed many other differ-
ences between the two species. M. leprae has only 1,600 genes,
compared with 4,000 genes in M. tuberculosis.16 The rest of
the genome appears to be cluttered with more than 1,100
pseudogenes, which resemble genes in M. tuberculosis, but are
no longer active. One clear conclusion from these results is that
the M. leprae genome is severely contracted (Figure 7.2). The
bacteria have lost many genes involved in metabolic pathways
and many enzymes. This massive gene decay is unprecedented
in sequenced genomes and likely explains why the leprosy
bacillus is so resistant to artificial culture. It might also provide
a reason for the unusually long division time for the bacteria.
Scientists have made some progress in understanding the
interaction of these bacteria with their preferred host cells—
Schwann cells. Schwann cells are present in the peripheral

HOW DO BACTERIA LOOK IN THE LAB?

Bacteria are grown on solid media that contain peptone,
yeast extract, and sodium chloride (yes, even bacteria like
common table salt). These components are mixed in water
and then agar is added to solidify the media. After mixing
all these things together, the mixture is autoclaved
(boiled under high pressure to kill all living organisms).
Then, the media is ready. It is poured into dishes, allowed
to set, and used for growing bacteria. Starting from
a very small number of bacteria, it normally takes 12
to 16 hours to get a plate full of laboratory bacteria.
Unfortunately, things don’t work that fast for the
pathogenic bacteria.
 Understanding the M. leprae Bacillus 71

Figure 7.2 A schematic of the genome of Mycobacterium leprae

is shown here. The bacterium contains 1,600 genes.

nervous system and help to separate and insulate nerve cells.

Recent advances in culture techniques of Schwann cells and
Schwann cell/axon cultures have given rise to detailed investi-
gations of M. leprae Schwann cell interactions in vitro. These
studies may one day provide scientists with vaccine molecules
that help protect humans from leprosy.
8
Ongoing Reforms
and the Future
HAS THE SOCIAL STIGMA CHANGED?
Scientifically, leprosy is an infectious disease that can affect anyone. The
disease does not discriminate and is not a reflection of a patient’s moral
values or past sins. Unfortunately, this message is still not widely accepted
or understood. Like many other issues, education and empathy are
required in accepting leprosy-infected people into society. Many people
living in remote areas are still not able to accept patients back into their
lives. Most of those affected by the disease lead a normal healthy life after
treatment and do not pose a risk of transmitting the disease any further.
If, however, the infection has caused them any physical deformity or
disfigurement, patients can have a tough time fitting in with their families
and friends.
On the border of India and Nepal, leprosy patients who had been
shunned from society gathered together and made their living mainly by
begging. Their fate began to change in 1981, however, when reform efforts
in the name of The Little Flower Institution were started by Baba Christdas.
Little Flower is an institute for treating people with leprosy, helping them
to lead normal lives and earn an independent living. The colony began
with a hospital and doctors, for treatments. With time and financial
support, it now owns a cattle dairy and has a cotton-based handloom
industry where patients can work. When this effort was initiated, the
milk and textile products produced by Little Flower had a tough time
finding a market. Now, with increased public awareness, the dairy
producers can barely keep up with the market demand, allowing patients

72
 Ongoing Reforms and the Future 73

to recover from the disease and live with dignity and respect.
Many of these patients, however, come from poor, uneducated
families and societies, where they will have a difficult time
being accepted. The institute continues helping patients with
the following message: “Leprosy is a poor man’s disease, treat
the patients like other human beings.” 17

DIFFERENT WORLDWIDE EFFORTS

Leprosy is being managed at the global level by the World
Health Organization. In addition, various efforts at the
individual country level aim to curb the disease within given
political boundaries. The Indian Council for Medical Research
(ICMR) has many institutions dedicated to the study of leprosy,
from an epidemiological and drug discovery perspective. KIT
Biomedical Research Center in the Netherlands serves as a
knowledge center, giving advice to researchers, policy makers,
and health workers all over the world. The National Institute
of Health (NIH) has various research programs supporting
leprosy research in the United States. Similarly, there are
institutions in Nigeria (Leprosy Research Unit, eastern
Nigeria), and in Yemen (Yemen Leprosy Elimination Society).
In Brazil, the government has initiated an improved health
program. They have also started to educate the public through
the media, in an effort to decrease the social stigma associated
with leprosy (Figure 8.1).
In addition, the International Leprosy Elimination Program
(ILEP) promotes and facilitates cooperation between its
members by coordinating the different leprosy programs,
providing technical expertise, and representing the common
interests. ILEP is an international federation of different,
autonomous, nongovernment anti-leprosy organizations.

IS A VACCINE A POSSIBILITY?
During an invasion by a foreign organism, the body’s defense
mechanisms become quite active as they attempt to evade the
74 LEPROSY

Figure 8.1 Research and education helps to reduce, and even

eliminate, ignorance about leprosy. This sign, placed in the Gillis
W. Long Hansen’s Disease Center cemetery, shows that education
leads to acceptance.

attack and protect the body from becoming ill. It is important

to remember that the host-parasite relationship is a naturally
occurring and continuously evolving phenomenon. For every
defense that our body builds, parasites try to overcome it with
a modified strategy. It becomes important to artificially inter-
vene in this cycle, to prevent humans from further infection.
These interventions can function at two levels: prevention or
cure. A disease can be cured by killing the pathogen that caused
it, and by healing the damages caused by the invader.
 Ongoing Reforms and the Future 75

Another approach involves preventing the disease from

occurring in the first place. This is achieved by boosting the
body’s immune response, and preparing it against any future
infections. Successful vaccine candidates can be dead or inactive
pathogens (like the vaccines against polio and smallpox) or part
of the pathogen. There are vaccines available for bacterial
diseases like diphtheria, tetanus, pertussis (whooping cough),
tuberculosis, and typhoid fever. The BCG vaccine that is used for
tuberculosis has also been tried for leprosy. It has been reported
to be partially effective against the disease. A worldwide BCG
vaccination program against M. leprae is not economically
feasible, however. There have been some other vaccine trials
using different combinations of heat-killed M. leprae and BCG,
with some Mycobacterium isolates that can be grown in the
laboratory. Results of these studies have been mixed, however,
and not absolutely protective. In the absence of a successful
vaccine candidate, MDT remains the only adequate weapon
against M. leprae.

WHAT IS THE WORLD

HEALTH ORGANIZATION?
The World Health Organization (WHO) is the United Nations’
specialized agency for health. Established in 1948, the
WHO’s mission is the attainment of the highest possible
level of health for all people worldwide. Health, as defined
by the WHO, is a state of complete physical, mental, and
social well-being, and not merely the absence of disease
or infirmity.
The WHO is governed by 192 member states through the
World Health Assembly. The Health Assembly is composed
of representatives from the WHO’s member states. The WHO
member states are grouped into six regions, each with its
own regional office.
76 LEPROSY

Efforts are underway to find the bacterial components (cell

wall and bacterial membrane) that can elicit a strong immune
response in the body, to keep it prepared to fight any future
attack. Such components can serve as successful vaccines.
Leprosy has been largely eradicated from Europe, North
America, and Japan, as living conditions have improved for
the general population and as potable water, sanitation, and
adequate nutrition have become accessible to people in all
social classes. Global attempts are underway to eliminate
the leprosy bacteria. The slow growth of the pathogen, the
apparent lack of environmental or animal reservoirs, low
infectivity, and availability of effective therapy make it an ideal
target for elimination.

NEW DRUGS AND THE FUTURE

Multi-drug therapy, which is currently in use, has proven the
most effective way to fight this disease. The search for new
drugs, however, continues. An attempt to identify drugs that
can stop the neural damage caused by the bacteria will be a
great help. Bacteria recognize certain molecules on the host
cells’ surface, which helps in binding. After identifying the
right target cell, the bacteria bind to some proteins and enter
a new home. Attempts are underway to understand the host
cell molecules that may help in bacterial entry. Some host cell
proteins, like dystroglycan, belonging to the family of glyco-
proteins, have already been identified as potential binding
molecules. Any drug that can prevent binding of the bacteria
to these host molecules will prevent entry of bacteria into the
nerve cell, stopping any subsequent neural damage.
Researchers are working to find more host proteins,
which are essential for the bacterial infection in our bodies.
The ultimate goal is to find new targets for drugs. In addition,
the continuous hunt for new drug targets can provide backup,
in the event the bacteria develop drug resistance to the exist-
ing mechanisms.
 Ongoing Reforms and the Future 77

Nerve damage and the resulting disabilities are the major

cause of morbidity among leprosy patients. These damages can
cripple a patient for the rest of their lives, even after being cured
of the disease. Different preventive procedures (management
of reactions, nerve decompression) and corrective procedures
(tendon transfers, management of plantar ulcers) are available
to manage deformities. In addition, the availability of surgery,
timely physiotherapy, and health education are very important
in the prevention, management, and rehabilitation resulting
from the disabilities associated with the disease. As leprosy
patients continue to experience disabilities, these services will
continue to be required. Compassion has never been more
necessary than it is in the fight against this disease.
Glossary
Acid fast staining—A staining procedure that differentiates between
bacteria, based on their ability to retain a dye when washed with an acid-
alcohol solution.
Anaesthetic—Unable to sense touch, heat, cold, or pain.
Antigens —Any foreign particle that, upon entering our body, can cause
an immune response.
Antigen receptor—Protein molecules that look similar to antibodies, found
on the surface of specialized immune cells.
AIDS (acquired immune deficiency syndrome)—A disease caused by the
HIV virus.
Apoptosis—Programmed cell death; normal process in which cells perish in
an orderly, highly controlled manner in order to sculpt and control an
organism’s development.
Autoclave—An apparatus for sterilizing objects through the use of steam
under pressure.
Bioinformatics—The application of computer science to the interpretation
and management of biological data.
Biopsy—A small tissue sample.
Borderline leprosy—This form of the disease is characterized by the presence
of single or multiple skin lesions with ill-defined or indistinct borders.
Many satellite lesions emerge around the larger ones. As suggested by the
name, the nerve structure shows an intermediate kind of pathology, with
some damage, but not as much as is seen in the tuberculoid form.
Cell mediated immunity—A type of immunity that operates through a type
of white blood cell called a T cell. During cell-mediated immune responses,
cells that can destroy other cells become active. Their destructive activity is
limited to cells that are either infected with, or are producing, a specific antigen.
Cytotoxic—Having a toxic, or deadly, effect on cells.
Endemic—Native to, or restricted to a given place or population.
Gangrenous—Containing dead soft tissue, due to loss of blood supply.
Genomic sequencing—The sequencing of all DNA.
Granulomas—Masses or nodules of chronically inflamed tissue, which are
usually associated with an infective process.

78
Humoral immunity—Type of immunity that principally operates through a
type of white blood cell called a B cell, which originates in bone marrow
and the spleen. During humoral immune responses, proteins called anti-
bodies, which can stick to and destroy antigens, appear in the blood and
other body fluids.
Hyperpigmented—Areas of skin that become darker or redder than the rest
of the skin.
Hypopigmented—Areas of skin that get discolored or lose their normal
color.
Laminin—A protein specifically found in nerve tissue.
Leonine facies—Lion-like facial features.
Leprologist—A physician experienced in the study and treatment of leprosy.
Lepromatous leprosy—The more easily spread of the two forms of leprosy.
This more severe form produces large disfiguring nodules.
Macrophages—Specialized immune cells that can engulf other cells or
pathogens.
Major histocompatibility complex (MHC)—A set of cellular surface proteins/
antigens that are specific for an organism and play a major role in identi-
fying similar tissue and rejecting tissue from other organisms.
Morbidity—Illness or suffering caused by a disease.
Mortality—Deaths caused by a disease or any other agent.
Multibacillary leprosy—See lepromatous leprosy.
Neuropathy—A disease or abnormality of the neural system.
Nucleus—The eucaryotic cell organelle that is surrounded by a double
membrane and contains all of that cell’s genetic material.
Obligate intracellular parasite—A parasite which cannot survive outside a
living cell.
Osmotic lysis—Rupturing of a cell when placed in a dilute environment.
Paleobiologists—Scientists who study the biology of fossil organisms.
Paleo-epidemiologists—Scientists who study disease in fossil organisms.
Papule—A small, solid, often inflammed elevation of the skin that does not
contain pus.

79
Glossary
Pasteurization—The process of heating milk and other liquids to destroy
microorganisms that can cause spoilage or disease.
Paucibacillary leprosy—Type of leprosy in which the nerve architecture is
destroyed and in which there can be formation of granulomas in nerves.
Peptidoglycan—A large polymer composed of long polysaccharide chains
that are linked to each other. They provide much of the strength and
rigidity of the bacterial cell walls.
Phagocytosis—The engulfing, and usually the destruction of particulate
matter by phagocytes.
Polymerase chain reaction (PCR)—An in vitro technique used to synthesize
large quantities of specific nucleotide sequences from small amounts of
DNA.
Prokaryote—Organisms that lack a true membrane bound nucleus.
Pseudogenes—Parts of DNA; similar to genes of other organisms but are
not functional.
Ribosome—The organelle where protein synthesis occurs.
Schwann cell—A type of glial cell of the peripheral nervous system that helps
separate and insulate nerve cells.
Thymus—A small glandular organ located behind the breastbone.
Transfer RNA (tRNA)—A small RNA that binds an amino acid and delivers it
to the ribosome for protein synthesis.
Tuberculoid leprosy—The more benign type of leprosy that affects the
nerves; often leads to numbness (usually of the extremities). Affects the
peripheral nerves and, sometimes, the surrounding skin on the face, arms,
legs, and buttocks.

80

CHAPTER 1:
HISTORICAL OVERVIEW
1 “Leprosy: History and Incidence,”
Encyclopedia.com. Available online at
http://www.encyclopedia.com/html/sec
tion/leprosy_HistoryandIncidence.asp
2 The Leprosy Mission International,
Available online at http://www
.leprosymission.org
3 Leprosy Sufferers Need Compassion,
“Forum on Leprosy.” Available online
at http://www.webspawner.com/
users/LEPROSY/
CHAPTER 3:
LEPROSY AROUND
THE WORLD
4 Sharon Lerner. “Cases of leprosy on
the rise in U.S.,” The New York Times,
February 20, 2003, available online at
International Herald Tribune,
http://www.iht.com/articles/
87291.html
5 World Health Organization
International. “Elimination of Leprosy
as a Public Health Problem.” Available
online at http://www.who.int/lep/
6 American Leprosy Missions. “Angola:
Facts.” Available online at http://www
.leprosy.org/PROJangola.html
7 Ibid.
8 World Health Organization
International. “Global Leprosy
Situation.” Available online at
http://www.cefpas.it/fad/fad/
1global.htm
9 Ibid.
10 World Health Organization
International. “Weekly epidemiological
record.” January 4, 2002. Available
online at http://www.who.int/
docstore/wer/pdf/2002/wer7701.pdf
Notes
11 World Health Organization
International. “Global Leprosy
Situation.” Available online at
http://www.cefpas.it/fad/fad/
1global.htm
CHAPTER 6:
CONTROLLING
THE DISEASE
12 “Leprosy research in the post-genome
era”. Available online at http://www
.lepra.org.uk/review/Mar01/pp8-22.pdf
13 Ibid.
14 American Cancer Society.
“Thalidomide Makes News Again:
New Research on How Thalidomide
May Help the Cancer Patients.”
October 6, 1998. Available online at
http://www.cancer.org/docroot/NWS/
content/NWS_1_1x_Thalidomide_
Makes_News_Again.asp
CHAPTER 7:
UNDERSTANDING THE
M. LEPRAE BACILLUS
15 San Francisco State University,
Department of Geography. “The
Biogeography of the Nine-Banded
Armadillo,” December 7, 1999.
Available online at http://bss.sfsu.edu/
geog/bholzman/courses/fall99projects/
armadillo.htm
16 Cole ST et al. “Massive gene decay in
the leprosy bacillus” Nature 2001, 409:
1007–1011
CHAPTER 8:
ONGOING REFORMS
AND THE FUTURE
17 “Baba Changing the Lives of
Ostracized Lepers.” Available online at
http://www.brightindia.com/mymite
.html
81
Bibliography
American Cancer Society. “Thalidomide Makes News Again: New Research
on How Thalidomide May Help the Cancer Patients.” October 6, 1998.
Available online at http://www.cancer.org/docroot/NWS/content/NWS
_1_1x_Thalidomide_Makes_News_Again.asp
American Leprosy Missions. “Angola: Facts.” Available online at http://www
.leprosy.org/PROJangola.html
“Baba Changing the Lives of Ostracized Lepers.” Available online at
http://www.brightindia.com/mymite.html
“Leprosy: History and Incidence.” Encyclopia.com. Available online at
http://www.encyclopedia.com/html/section/leprosy_HistoryandIncidence
.asp
Leprosy Mission International. Available online at http://www.leprosymission
.org
“Leprosy research in the post-genome era.” Available online at http://www
.lepra.org.uk/review/Mar01/pp8-22.pdf
Leprosy Sufferers Need Compassion. “Forum on Leprosy.” Available online at
http://www.webspawner.com/users/LEPROSY/
Lerner, Sharon. “Cases of leprosy on the rise in U.S.” The New York Times,
February 20, 2003, available online at International Herald Tribune,
http://www.iht.com/articles/87291.html
San Francisco State University. Department of Geography. “The
Biogeography of the Nine-Banded Armadillo.” December 7, 1999.
Available online at http://bss.sfsu.edu/geog/bholzman/courses/fall99
projects/armadillo.htm
World Health Organization International. “Elimination of Leprosy as a Public
Health Problem.” Available online at http://www.who.int/lep/
———. “Global Leprosy Situation.” Available online at http://www.cefpas.it/
fad/fad/1global.htm
———. “Weekly epidemiological record.” January 4, 2002. Available online at
http://www.who.int/docstore/wer/pdf/2002/wer7701.pdf

82
 Further Reading
ADe Mallac, M.J. Hansen’s Disease: The Shared Paradigm: East Sussex,
England: Book Guild, Ltd, 2001.
Donnelly, Karen. Leprosy. New York: Rosen Publishing Group, 2001.
Farrow, John. Damien the Leper. Image, 1998.
Gaudet, Marcia. Carville: Remembering Leprosy in America. Jackson, MS:
University Press of Mississippi, 2004.
Job, C.K. Leprosy: Diagnosis and Management. New Dehli, India: Indian
Leprosy Association, 1975.
Kappor, P. Guide to Leprosy and Leprosy Control. India: J.M. Mehta, 1977.
Stewart, Richard. Leper Priest of Moloka’i: The Father Damien Story.
Honolulu: HI: University of Hawaii Press, 2000.

83
Websites
American Leprosy Missions
http://www.leprosy.org/
World Health Organization—Leprosy Information
http://www.who.int/lep/
Centers for Disease Control—Hansen’s Disease (Leprosy)
http://www.cdc.gov/ncidod/dbmd/diseaseinfo/hansens_t.htm

84
 Index
Acid-fast, 39 Cell wall Humoral immunity,
Acquired immune defi- components, 38–43 46–47, 49, 79
ciency syndrome function, 40 Hyperpigmented, 56
(AIDS), 33 Cholera, 23 Hypopigmented, 56
discovery of, 9, 37 Clofazimine, 58 lesions, 23, 28
Acquired immunity, 46–47 Cytotoxic, 49
Adaptive immunity, 46 Immune system
AIDS. See Acquired Danielsen, Daniel components of, 47–51
immune deficiency Cornelius, 13 functions, 45–46
syndrome DDS. See Diamino response, 27, 45–49,
Anaesthetic, 23 diphenyl sulphone 51–55, 60, 75–76
Antibodies, 47, 49, 57 De Veuster, Damien weakened, 37
Antigen, 45, 47 Joseph (Father Immunity
presenting cells, 51 Damien), 23, 25 to leprosy, 9, 23, 53–54
receptor, 49–51 Diagnosis, leprosy, 10, types, 45–49
Apoptosis, 54 22, 56–57, 59 Indian Council for
Armadillos Diamino diphenyl sul- Medical Research, 73
advantages of, 66–70 phone (DDS), 58 Innate immunity, 46, 48
bacteria in, 31, 43, Diphtheria, 75 Infectious diseases
66–67, 70 Domack, Gerhardt, 58 types, 9, 33–34, 72, 75
Autoclave, 70 Influenza, 23
Endemic International Leprosy
Bacillus Calmette Guérin of leprosy, 10–11, 17, Elimination Program,
(BCG), 31, 75 33, 69 73
Bacteria Epidemic
colors, 42–43 of leprosy, 16, 33 Koch, Robert, 13, 39
and disease, 8–9, Escherichia coli, 64–65 Kushtha. See Leprosy
11–13, 23, 25, 27,
31, 35, 37, 39, 42, Faget, Dr. Guy, 58–59 Laminin, 51
44–46, 48, 51, 53, Leonine facies, 29
57, 60, 63–66, Gangrene, 9 Leper Act (1898), 19
69–71, 75–76 Genome Leprologist, 51
resistant, 41 sequencing, 69–71 Leprosy
structures, 35, 38–42, Gram, Christian, 42 around the world, 21,
70 Gram staining method, 31–34, 73
Bailey, Alice Grahame, 39, 42–43 causes, 8, 12, 19, 23,
18–19 Granuloma, 29 31, 35–44, 56, 69
Bailey, Wellesley, 18–19, characteristics, 33–34,
58 Hansen, Gerhard 57
BCG . See Bacillus Armauer complications, 11
Calmette Guérin and the discovery of control of, 56–63
Bioinformatics, 69 leprosy, 12–13, 19 discovery of, 13
Biopsy, 56–57 Hansen’s disease. See history of, 8–20
Borderline leprosy, 29, 54 Leprosy social stigma, 8, 10, 12,
Hemorrhagic fever, 34 14–17, 21, 33–34,
Cell mediated immunity Host-pathogen interac- 60, 63, 72–73, 77
(CMI), 46–47, 52, 54–55 tions, 45–55, 70, 76 types, 27–30, 53–54

85
Index
Leprosy Mission Pasteurization, 37 risk, 72
International, 19 Paucibacillary leprosy, 29 unsanitary conditions
Lepromatous leprosy, 27, PCR. See Polymerase and, 9, 23
29–30, 53–54 chain reaction Treatment, leprosy, 8, 13,
Little Flower Institution, Peptidoglycan, 40, 43 72
72–73 Pertussis. See Whooping chaulmoogra oil, 17–18,
Lymphocytes, 50 cough 20, 57–58
T cells, 49, 51, 54–55 Phagocytosis, 49 drugs, 10–11, 21, 31,
Polymerase chain reaction 58–60, 63, 67,
Macrophages, 46, 48–49, (PCR), 34, 57 76–77
51–52 Prevention, leprosy history, 17–20
Major histocompatibility education, 72–74 isolation, 23
complex (MHC), 51 research, 75–77 multi-drug, 58–59, 63,
Malaria, 6, 33–34 Prokaryote, 35 75
Meningitis, 6 Promin, 59 and recovery, 22
MHC. See Major histo- Pseudogenes, 70 and research, 57–63,
compatibility complex 67, 69–71, 73
Morbidity Ribosomes, 35 Tuberculoid leprosy,
of leprosy, 77 Rifampicin, 58 27–30, 53–54
Mouat, Dr. J.F., 18 Tuberculosis, 33–34, 39,
Multibacillary leprosy. See Schwann cells, 51–54, 70–71 75
Lepromatous leprosy Signs and symptoms, causes and transmis-
Mycobacterium leprae leprosy, 8, 21, 57 sion, 8–9, 13, 35,
in the body, 12, 45, anaesthesia, 9, 11, 23, 37, 39
51–55 29 symptoms and treat-
characteristics, 37–39, blindness, 27 ment, 39
42–44, 64–71 deformities, 9, 27, 31, Typhoid fever, 75
discovery, 13, 31 59–60, 63, 72, 77
and leprosy, 8, 18–19, hypopigmented spot, Vaccines
22, 31, 37–39, 63, 11, 23–24 and leprosy, 31, 44, 67,
69–71, 75 muscle weakness, 25, 71, 73–76
targets of, 51 27, 29 Viruses, 45, 47
nerve damage, 9, 24–25,
National Institute of 27, 29–30, 55–56, Whooping cough
Health (NIH), 73 63, 77 (Pertussis), 33
Neuropathy, 29 rash, 10–12, 27–29, 60 WHO. See World Health
Organization
Obligate intracellular Thalidomide, 60 World Health Organiza-
parasite, 44 Thymus, 47 tion (WHO)
Osmotic lysis, 40 Transmission, leprosy, efforts of, 11, 31–33,
22–23, 69 58, 73, 75
Paleobiologists, 41 history, 16
Paleo-epidemiologists, 41 infected soil, 23 Zeihl-Neelsen staining
Papule, 29 respiratory, 8–9, 11, 22 method, 39

86
 Picture Credits
14: © Werner Forman/Art Resource, NY 43: © Jack Bostrack/Visuals Unlimited
20: National Library of Medicine 48: © Peter Lamb
24: © CORBIS 50: © Dr. David M. Phillips/Visuals Unlimited
26: © Emmanuel Kwitema/Reuters/CORBIS 53: © Peter Lamb
28: © WHO/P. Virot 59: © Bettmann/CORBIS
36: (top and bottom) © Dr. Dennis Kunkel/ 61: © Peter Lamb
Visuals Unlimited 62: © Bettmann/CORBIS
38: Courtesy Public Health Image Library 68: © Philip Gould/CORBIS
(PHIL), CDC 71: © Peter Lamb
40: © Peter Lamb 74: © Najlah Feanny/CORBIS SABA

Cover: © Dr. John Cunningham/Visuals Unlimited

87
About the Author
Alfica Sehgal, Ph.D., is currently completing her postdoctoral research at
Johns Hopkins Medical School in Baltimore Maryland. She received her
Ph.D. in molecular parasitology from Tata Institute of Fundamental Research
in Mumbai, India. She received her first postdoctoral research training at Yale
University School of Medicine in New Haven, Connecticut. During her Ph.D.
and post-doctoral training, she performed extensive molecular level research
on parasites like Plasmodium and Toxoplasma. Sehgal is interested in study-
ing the basic biological mechanisms in different organisms and applying that
knowledge to improve pharmacological and diagnostic methods.

About the Founding Editor

The late I. Edward Alcamo was a Distinguished Teaching Professor of
Microbiology at the State University of New York at Farmingdale. Alcamo
studied biology at Iona College in New York and earned his M.S. and Ph.D.
degrees in microbiology at St. John’s University, also in New York. He had
taught at Farmingdale for over 30 years. In 2000, Alcamo won the Carski
Award for Distinguished Teaching in Microbiology, the highest honor for
microbiology teachers in the United States. He was a member of the American
Society for Microbiology, the National Association of Biology Teachers,
and the American Medical Writers Association. Alcamo authored numerous
books on the subjects of microbiology, AIDS, and DNA technology as well
as the award-winning textbook Fundamentals of Microbiology, now in its
sixth edition.

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